Inducible co-stimulator (ICOS) belongs to CD28 and CTLA-4 cell-surface receptor family and is bro... more Inducible co-stimulator (ICOS) belongs to CD28 and CTLA-4 cell-surface receptor family and is broadly expressed in activated T cells. ICOS has been shown to regulate the interactions between T and B cells. However, the role of ICOS in the induction of regulatory T cells (Tregs) by allogeneic CD40-activated B cells remains to be clarified. In this study, we assayed the expressions of ICOS and ICOSL in CD4+ and CD8+ Tregs induced by CD40-activated B cells and examined the roles of them in the generation and function of these Tregs. With the blockade of ICOS-ICOSL interaction by ICOS-Ig, we found that the generation of both CD4+ and CD8+ Tregs was significantly decreased as compared to control. Interestingly, this blockade during the induction of Tregs only abolished the suppressive capacity of CD4+ Tregs but did not affect the suppressive function of CD8+ Tregs. The loss of suppression in CD4+ Tregs was related to the decrease of the surface expression of CTLA-4 in CD4+ Tregs, which r...
Although the health risks of cigarette smoke are widely reported, the impact and mechanism of sho... more Although the health risks of cigarette smoke are widely reported, the impact and mechanism of short-term cigarette smoke exposure on inflammatory diseases are still unclear. Until now, there is no study about the role of cigarette smoke in 2009 pandemic H1N1 and avian influenza A H9N2 infection. Based on our previous study, which investigated the mouse mortality, weight changes, lung virus loads and inflammatory cytokines and chemokines’ expression, we further analyzed the status of inflammatory responses before the virus infection, pulmonary histological analysis and the lung cell profiles after virus infection. Mild inflammatory responses were shown before influenza A virus infection after cigarette smoke exposure. For pdmH1N1 infection, although there was a trend that smoke exposure group had a lower lung inflammatory score and less neutrophils infiltrated into the lung than the air exposure group, the difference was not significant. However, after H9N2 virus infection, the mice ...
Influenza remains a global threat to public health. There are few antiviral drugs for treating in... more Influenza remains a global threat to public health. There are few antiviral drugs for treating influenza and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Pamidronate has been commonly used to treat osteoporosis by enhancing human Vγ9Vδ2-T-cell immunity. Using Rag2-/-γc-/- mice reconstituted with human peripheral mononuclear cells (huPBMCs) as a model, we demonstrate that the treatment of pamidronate decreases disease severity and/or mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. Importantly, pamidronate has no such effects in influenza virus-infected Rag2-/-γc-/- mice reconstituted with Vγ9Vδ2-T-cell-depleted huPBMCs. Our results demonstrate that pamidronate can control...
Cigarette smoke has both immune-activating and suppressing activities. Mouse studies have demonst... more Cigarette smoke has both immune-activating and suppressing activities. Mouse studies have demonstrated that smoke exposure increases the expressions of some factors likely to be important in the antiviral defense. However, there is no report about the role of cigarette smoke in 2009 pandemic H1N1 (pdmH1N1) and avian influenza A H9N2 (H9N2/G1) infection. In this study, C57/B6N mice were whole body exposed to 4% cigarette smoke 4 hours per day for 21 days and then infected with pdmH1N1 or H9N2 virus. Some mice were exposed to room air in parallel as the control group. Mortality, weight changes, lung virus loads and inflammatory cytokines and chemokines were analyzed. For pdmH1N1 infection, although no significant difference in the lung virus loads was shown between the two groups, smoke exposure group had a significantly lower mortality than the air exposure group, which may be caused by the lower inflammatory response in the smoke exposure group than in the air exposure group at day ...
We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobr... more We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N = 116) and CoronaVac (CC, N = 123) versus adults after 2 doses of the same vaccine (BB, N = 147; CC, N = 141) but not in adolescents after 1-dose BNT162b2 (B, N = 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, ...
Background The protective effect of T cell-mediated immunity against influenza virus infections i... more Background The protective effect of T cell-mediated immunity against influenza virus infections in natural settings remains unclear, especially in seasonal epidemics. Methods To explore the potential of such protection, we analyzed the blood samples collected longitudinally in a community-based study and covered the first wave of pandemic H1N1 (pH1N1), two subsequent pH1N1 epidemics, and three seasonal H3N2 influenza A epidemics (H3N2) for which we measured pre-existing influenza virus-specific CD4 and CD8 T cell responses by intracellular IFN-γ staining assay for 965 whole blood samples. Results Based on logistic regression, we found that higher pre-existing influenza virus-specific CD4 and CD8 T cell responses were associated with lower infection odds for corresponding subtypes. Every fold increase in H3N2-specific CD4 and CD8 T cells was associated with 28% (95% CI 8%, 44%) and 26% (95% CI 8%, 41%) lower H3N2 infection odds, respectively. Every fold increase in pre-existing seaso...
Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost γδ-T cell immunity ha... more Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost γδ-T cell immunity has shown success in some cancer patients, the clinical application is limited due to the rapid exhaustion of Vγ9Vδ2-T cells caused by repetitive stimulation from phosphoantigens and the profoundly immunosuppressive tumor microenvironment (TME). In this study, using a cell culture medium containing human and viral interleukin-10 (hIL-10 and vIL-10) secreted from EBV-transformed lymphoblastoid B cell lines (EBV-LCL) to mimic the immunosuppressive TEM, we found that the antitumor activity of Vγ9Vδ2-T cells was highly suppressed by endogenous hIL-10 and vIL-10 within the TME. CD137 costimulation could provide an anti-exhaustion signal to mitigate the suppressive effects of IL-10 in TME by suppressing IL-10R1 expression on Vγ9Vδ2-T cells. CD137 costimulation also improved the compromised antitumor activity of Vγ9Vδ2-T cells in TME with high levels of IL-10 in Rag2-/- γc-/- mice. In humanized m...
Background: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to pub... more Background: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. Result: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining
The limited cytotoxicity of immune cells facilitates a successful establishment of pregnancy. How... more The limited cytotoxicity of immune cells facilitates a successful establishment of pregnancy. However, the association between cytotoxic granules and unexplained repeated implantation failure (uRIF) remains unkown. Twenty-one fertile controls and 54 patients with uRIF were included in this study. The pregnancy outcomes were monitored at different gestational periods. The peripheral blood lymphocytes were detected using specific monoclonal antibodies by flow cytometry. The percentage of perforin+ (Pfr+), granzyme B+ (GrB+), or granulysin+ (Gnly+) lymphocytes was not significantly different among fertile controls, uRIF patients with successful pregnancy outcomes, and uRIF patients with pregnancy failure. The percentage of GrB+ γδ-T cells in lymphocytes was markedly higher in uRIF patients with implantation failure and clinical pregnancy failure than that in uRIF patients with a corresponding successful pregnancy outcome. A four-tier risk model showed that the risk of suffering clinical pregnancy failure in uRIF patients among high risk tier (83.3 %), normal risk tier (65.0 %) and low risk tier (39.1 %) was elevated by 2-4 fold compared with uRIF patients among lowest risk tier (20.0 %). In addition, the percentage of GrB+ NK cells in lymphocytes tended to decrease in uRIF patients with pregnancy failure. The AUC of the combined indicator with GrB+ γδ-T cells and GrB+ NK cells was increased than that of GrB+ γδ-T cells and GrB+ NK cells for predicting clinical pregnancy failure. In conclusion, the frequency of GrB-expressing γδ-T and NK cells in peripheral blood could serve as a predictor of clinical pregnancy failure in patients with uRIF.
BackgroundRadiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), b... more BackgroundRadiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), but its therapeutic efficacy is poor in some patients due to radioresistance. Adoptive T cell-based immunotherapy has also shown promise to control NPC; however, its antitumor efficacy may be attenuated by an immunosuppressive tumor microenvironment. Exosomes derived from γδ-T cells (γδ-T-Exos) have potent antitumor potentials. However, it remains unknown whether γδ-T-Exos have synergistic effect with radiotherapy and preserve their antitumor activities against NPC in an immunosuppressive tumor microenvironment.Methodsγδ-T-Exos were stained with fluorescent membrane dye, and their interactions with NPC were determined both in vitro and in vivo. NPC cell deaths were detected after treatment with γδ-T-Exos and/or irradiation. Moreover, effects of γδ-T-Exos on radioresistant cancer stem-like cells (CSCs) were determined. The therapeutic efficacy of combination therapy using γδ-T-Exos and irr...
Intravenous immunoglobulin has long been used in treating autoimmune diseases, although mechanism... more Intravenous immunoglobulin has long been used in treating autoimmune diseases, although mechanisms remain uncertain. Activating Fcc receptors are receptors of IgG and reported to be essential in intravenous immunoglobulin (IVIG) therapy. Therefore, we hypothesized natural killer (NK) cells, which express abundant activating Fcc receptors, are the potential cellular target. In experimental autoimmune encephalomyelitis (EAE), we demonstrated that IgG suppressed disease development in intact, but not in NK cell depleted mice. Adoptive transfer of IgG-treated NK cell could protect mice against EAE, and suppressed interferon c and interleukin 17 production. The percentage of CD4+Foxp3+ regulatory T cells was significantly increased. The increase of regulatory T cells was also observed in IgG-treated EAE mice but not in NK cell depleted mice. In vitro experiments confirmed that IgG-treated NK cells enhanced regulatory T cell induction from naı̈ve CD4+ T cells. Interestingly, cells from dr...
In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46 + NKG2A + NK cell subset ... more In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46 + NKG2A + NK cell subset induced by influenza A virus infection. These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection.
The abstract can be viewed at: http://www.hkjpaed.org/pdf/2014;19;100-128.pdfBackground and aims:... more The abstract can be viewed at: http://www.hkjpaed.org/pdf/2014;19;100-128.pdfBackground and aims: Genetic defects in IFNγ/IL12 pathway causes susceptibility to severe infections with mycobacteria and fungi. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor involved in this signaling pathway. It is crucial in interferon-mediated immunity against microbial infections by regulating the expressions of IFN responsive genes. Chronic mucocutaneous candidiasis is a heterogeneous group of primary immunodeficiency diseases characterised by Candida infections of the skin and oropharynx. STAT1 gainof-function mutation was shown to be responsible for autosomal-dominant cases of chronic candidiasis. In contrast, STAT1 loss-of-function mutations have been mostly reported in patients with atypical mycobacterial and Salmonella infection. Herein we sought to investigate the STAT1 mutation in a patient who presented with not only recurrent candidiasis, but also mycobacterial infection. Methods: Exome sequencing was performed for this patient. After bioinformatical analysis, STAT1 was sequenced by Sanger sequencing. The STAT1 signaling pathway including IFN-stimulated STAT1 phosphorylation, transcriptional response and target gene expressions were examined. Results: The patient was a Chinese girl born to nonconsanguineous parents. Since infancy she presented with recurrent oropharyngeal and perineal candidiasis that was refractory to antifungal treatment, and also had recurrent Salmonella gastroenteritis. At 5 years old, she developed granulomatous lymphadenitis caused by Mycobacterium fortuitum. At 14 months she developed type 1 diabetes mellitus and was treated with insulin. Exome sequencing identified a novel autosomal dominant loss-of-function E559K mutation in the linker domain of STAT1, which was confirmed by Sanger sequencing. The mutation impaired phosphorylation induced by both IFNγ and IFNα, leading to decreased expressions of interferon inducible target genes. STAT1 protein expression was not affected. Conclusions: In addition to mycobacterial infection, STAT1 loss-of-function mutation also predisposes to chronic mucocutaneous candidiasis, likely through aberrant regulation of IFN-mediated response. This extends the spectrum of clinical phenotype of STAT1 loss-of-function mutation. We also for the first time reported STAT1 mutation in the linker domain
Objective To investigate the effects of insulin-like growth factor 1 (IGF-1) on neonatal immunity... more Objective To investigate the effects of insulin-like growth factor 1 (IGF-1) on neonatal immunity. Methods Cord blood mononuclear cells (CBMC) from 10 normal, full-term infants, and 10 adults' peripheral blood mononuclear cells (PBMC, controls) were involved in this study. CBMC and PBMC were cultured in a serum and hormone-free medium. Cytokine activity was measured by ELISA. Results Compared with that of adults, the productions of IL-2, IL-4 and IFN-γ in PHA-stimulated CBMC were significantly decreased, and the productions of IL-10 and IL-12 in LPS-stimulated CBMC were also significantly reduced. IGF-1 alone could not induce IL-2, IL-4, IFN-y and IL-10 productions in CBMC or PBMC. However, it could induce a high level of IL-6 production and a low level of IL-12 production in CBMC or PBMC. IGF-1 significantly increased the productions of both IL-6 and IFN-γ in PHA-stimulated neonatal MNC. Moreover, it increased neonatal IFN-γproduction in PHA-stimulated CBMC to a level similar t...
Zhonghua er ke za zhi = Chinese journal of pediatrics, 2010
自2009年4月北美首次發現甲型H1N1流感病毒以來,該新型豬源病毒已播散至全球,引起21世紀首次流感大流行,對人類健康產生巨大威脅[1-2].與季節性流感不同,本次甲型H1N1流感大流行是由一... more 自2009年4月北美首次發現甲型H1N1流感病毒以來,該新型豬源病毒已播散至全球,引起21世紀首次流感大流行,對人類健康產生巨大威脅[1-2].與季節性流感不同,本次甲型H1N1流感大流行是由一種整合了古典豬流感、歐亞豬流感、禽流感和人季節性H3N2流感病毒基因的新型四源重組毒株引起.免疫系統包括先天性免疫和獲得性免疫系統,在構建了人體對流感病毒的防御體系的同時,也參與了流感病毒的致病機制.link_to_subscribed_fulltex
Inducible co-stimulator (ICOS) belongs to CD28 and CTLA-4 cell-surface receptor family and is bro... more Inducible co-stimulator (ICOS) belongs to CD28 and CTLA-4 cell-surface receptor family and is broadly expressed in activated T cells. ICOS has been shown to regulate the interactions between T and B cells. However, the role of ICOS in the induction of regulatory T cells (Tregs) by allogeneic CD40-activated B cells remains to be clarified. In this study, we assayed the expressions of ICOS and ICOSL in CD4+ and CD8+ Tregs induced by CD40-activated B cells and examined the roles of them in the generation and function of these Tregs. With the blockade of ICOS-ICOSL interaction by ICOS-Ig, we found that the generation of both CD4+ and CD8+ Tregs was significantly decreased as compared to control. Interestingly, this blockade during the induction of Tregs only abolished the suppressive capacity of CD4+ Tregs but did not affect the suppressive function of CD8+ Tregs. The loss of suppression in CD4+ Tregs was related to the decrease of the surface expression of CTLA-4 in CD4+ Tregs, which r...
Although the health risks of cigarette smoke are widely reported, the impact and mechanism of sho... more Although the health risks of cigarette smoke are widely reported, the impact and mechanism of short-term cigarette smoke exposure on inflammatory diseases are still unclear. Until now, there is no study about the role of cigarette smoke in 2009 pandemic H1N1 and avian influenza A H9N2 infection. Based on our previous study, which investigated the mouse mortality, weight changes, lung virus loads and inflammatory cytokines and chemokines’ expression, we further analyzed the status of inflammatory responses before the virus infection, pulmonary histological analysis and the lung cell profiles after virus infection. Mild inflammatory responses were shown before influenza A virus infection after cigarette smoke exposure. For pdmH1N1 infection, although there was a trend that smoke exposure group had a lower lung inflammatory score and less neutrophils infiltrated into the lung than the air exposure group, the difference was not significant. However, after H9N2 virus infection, the mice ...
Influenza remains a global threat to public health. There are few antiviral drugs for treating in... more Influenza remains a global threat to public health. There are few antiviral drugs for treating influenza and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Pamidronate has been commonly used to treat osteoporosis by enhancing human Vγ9Vδ2-T-cell immunity. Using Rag2-/-γc-/- mice reconstituted with human peripheral mononuclear cells (huPBMCs) as a model, we demonstrate that the treatment of pamidronate decreases disease severity and/or mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. Importantly, pamidronate has no such effects in influenza virus-infected Rag2-/-γc-/- mice reconstituted with Vγ9Vδ2-T-cell-depleted huPBMCs. Our results demonstrate that pamidronate can control...
Cigarette smoke has both immune-activating and suppressing activities. Mouse studies have demonst... more Cigarette smoke has both immune-activating and suppressing activities. Mouse studies have demonstrated that smoke exposure increases the expressions of some factors likely to be important in the antiviral defense. However, there is no report about the role of cigarette smoke in 2009 pandemic H1N1 (pdmH1N1) and avian influenza A H9N2 (H9N2/G1) infection. In this study, C57/B6N mice were whole body exposed to 4% cigarette smoke 4 hours per day for 21 days and then infected with pdmH1N1 or H9N2 virus. Some mice were exposed to room air in parallel as the control group. Mortality, weight changes, lung virus loads and inflammatory cytokines and chemokines were analyzed. For pdmH1N1 infection, although no significant difference in the lung virus loads was shown between the two groups, smoke exposure group had a significantly lower mortality than the air exposure group, which may be caused by the lower inflammatory response in the smoke exposure group than in the air exposure group at day ...
We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobr... more We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N = 116) and CoronaVac (CC, N = 123) versus adults after 2 doses of the same vaccine (BB, N = 147; CC, N = 141) but not in adolescents after 1-dose BNT162b2 (B, N = 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, ...
Background The protective effect of T cell-mediated immunity against influenza virus infections i... more Background The protective effect of T cell-mediated immunity against influenza virus infections in natural settings remains unclear, especially in seasonal epidemics. Methods To explore the potential of such protection, we analyzed the blood samples collected longitudinally in a community-based study and covered the first wave of pandemic H1N1 (pH1N1), two subsequent pH1N1 epidemics, and three seasonal H3N2 influenza A epidemics (H3N2) for which we measured pre-existing influenza virus-specific CD4 and CD8 T cell responses by intracellular IFN-γ staining assay for 965 whole blood samples. Results Based on logistic regression, we found that higher pre-existing influenza virus-specific CD4 and CD8 T cell responses were associated with lower infection odds for corresponding subtypes. Every fold increase in H3N2-specific CD4 and CD8 T cells was associated with 28% (95% CI 8%, 44%) and 26% (95% CI 8%, 41%) lower H3N2 infection odds, respectively. Every fold increase in pre-existing seaso...
Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost γδ-T cell immunity ha... more Although γδ-T cell-based tumor immunotherapy using phosphoantigens to boost γδ-T cell immunity has shown success in some cancer patients, the clinical application is limited due to the rapid exhaustion of Vγ9Vδ2-T cells caused by repetitive stimulation from phosphoantigens and the profoundly immunosuppressive tumor microenvironment (TME). In this study, using a cell culture medium containing human and viral interleukin-10 (hIL-10 and vIL-10) secreted from EBV-transformed lymphoblastoid B cell lines (EBV-LCL) to mimic the immunosuppressive TEM, we found that the antitumor activity of Vγ9Vδ2-T cells was highly suppressed by endogenous hIL-10 and vIL-10 within the TME. CD137 costimulation could provide an anti-exhaustion signal to mitigate the suppressive effects of IL-10 in TME by suppressing IL-10R1 expression on Vγ9Vδ2-T cells. CD137 costimulation also improved the compromised antitumor activity of Vγ9Vδ2-T cells in TME with high levels of IL-10 in Rag2-/- γc-/- mice. In humanized m...
Background: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to pub... more Background: Rapid Advice Guidelines (RAG) provide decision makers with guidance to respond to public health emergencies by developing evidence-based recommendations in a short period of time with a scientific and standardized approach. However, the experience from the development process of a RAG has so far not been systematically summarized. Therefore, our working group will take the experience of the development of the RAG for children with COVID-19 as an example to systematically explore the methodology, advantages, and challenges in the development of the RAG. We shall propose suggestions and reflections for future research, in order to provide a more detailed reference for future development of RAGs. Result: The development of the RAG by a group of 67 researchers from 11 countries took 50 days from the official commencement of the work (January 28, 2020) to submission (March 17, 2020). A total of 21 meetings were held with a total duration of 48 h (average 2.3 h per meeting) and an average of 16.5 participants attending. Only two of the ten recommendations were fully supported by direct evidence for COVID-19, three recommendations were supported by indirect evidence only, and the proportion of COVID-19 studies among the body of evidence in the remaining
The limited cytotoxicity of immune cells facilitates a successful establishment of pregnancy. How... more The limited cytotoxicity of immune cells facilitates a successful establishment of pregnancy. However, the association between cytotoxic granules and unexplained repeated implantation failure (uRIF) remains unkown. Twenty-one fertile controls and 54 patients with uRIF were included in this study. The pregnancy outcomes were monitored at different gestational periods. The peripheral blood lymphocytes were detected using specific monoclonal antibodies by flow cytometry. The percentage of perforin+ (Pfr+), granzyme B+ (GrB+), or granulysin+ (Gnly+) lymphocytes was not significantly different among fertile controls, uRIF patients with successful pregnancy outcomes, and uRIF patients with pregnancy failure. The percentage of GrB+ γδ-T cells in lymphocytes was markedly higher in uRIF patients with implantation failure and clinical pregnancy failure than that in uRIF patients with a corresponding successful pregnancy outcome. A four-tier risk model showed that the risk of suffering clinical pregnancy failure in uRIF patients among high risk tier (83.3 %), normal risk tier (65.0 %) and low risk tier (39.1 %) was elevated by 2-4 fold compared with uRIF patients among lowest risk tier (20.0 %). In addition, the percentage of GrB+ NK cells in lymphocytes tended to decrease in uRIF patients with pregnancy failure. The AUC of the combined indicator with GrB+ γδ-T cells and GrB+ NK cells was increased than that of GrB+ γδ-T cells and GrB+ NK cells for predicting clinical pregnancy failure. In conclusion, the frequency of GrB-expressing γδ-T and NK cells in peripheral blood could serve as a predictor of clinical pregnancy failure in patients with uRIF.
BackgroundRadiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), b... more BackgroundRadiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), but its therapeutic efficacy is poor in some patients due to radioresistance. Adoptive T cell-based immunotherapy has also shown promise to control NPC; however, its antitumor efficacy may be attenuated by an immunosuppressive tumor microenvironment. Exosomes derived from γδ-T cells (γδ-T-Exos) have potent antitumor potentials. However, it remains unknown whether γδ-T-Exos have synergistic effect with radiotherapy and preserve their antitumor activities against NPC in an immunosuppressive tumor microenvironment.Methodsγδ-T-Exos were stained with fluorescent membrane dye, and their interactions with NPC were determined both in vitro and in vivo. NPC cell deaths were detected after treatment with γδ-T-Exos and/or irradiation. Moreover, effects of γδ-T-Exos on radioresistant cancer stem-like cells (CSCs) were determined. The therapeutic efficacy of combination therapy using γδ-T-Exos and irr...
Intravenous immunoglobulin has long been used in treating autoimmune diseases, although mechanism... more Intravenous immunoglobulin has long been used in treating autoimmune diseases, although mechanisms remain uncertain. Activating Fcc receptors are receptors of IgG and reported to be essential in intravenous immunoglobulin (IVIG) therapy. Therefore, we hypothesized natural killer (NK) cells, which express abundant activating Fcc receptors, are the potential cellular target. In experimental autoimmune encephalomyelitis (EAE), we demonstrated that IgG suppressed disease development in intact, but not in NK cell depleted mice. Adoptive transfer of IgG-treated NK cell could protect mice against EAE, and suppressed interferon c and interleukin 17 production. The percentage of CD4+Foxp3+ regulatory T cells was significantly increased. The increase of regulatory T cells was also observed in IgG-treated EAE mice but not in NK cell depleted mice. In vitro experiments confirmed that IgG-treated NK cells enhanced regulatory T cell induction from naı̈ve CD4+ T cells. Interestingly, cells from dr...
In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46 + NKG2A + NK cell subset ... more In this study, we demonstrate a novel hemagglutinin (HA)-specific NKp46 + NKG2A + NK cell subset induced by influenza A virus infection. These memory NK cells show virus-specific decreased cytotoxicity and increased gamma interferon (IFN-γ) on reencountering the same influenza virus antigen. In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection.
The abstract can be viewed at: http://www.hkjpaed.org/pdf/2014;19;100-128.pdfBackground and aims:... more The abstract can be viewed at: http://www.hkjpaed.org/pdf/2014;19;100-128.pdfBackground and aims: Genetic defects in IFNγ/IL12 pathway causes susceptibility to severe infections with mycobacteria and fungi. Signal transducer and activator of transcription 1 (STAT1) is a transcription factor involved in this signaling pathway. It is crucial in interferon-mediated immunity against microbial infections by regulating the expressions of IFN responsive genes. Chronic mucocutaneous candidiasis is a heterogeneous group of primary immunodeficiency diseases characterised by Candida infections of the skin and oropharynx. STAT1 gainof-function mutation was shown to be responsible for autosomal-dominant cases of chronic candidiasis. In contrast, STAT1 loss-of-function mutations have been mostly reported in patients with atypical mycobacterial and Salmonella infection. Herein we sought to investigate the STAT1 mutation in a patient who presented with not only recurrent candidiasis, but also mycobacterial infection. Methods: Exome sequencing was performed for this patient. After bioinformatical analysis, STAT1 was sequenced by Sanger sequencing. The STAT1 signaling pathway including IFN-stimulated STAT1 phosphorylation, transcriptional response and target gene expressions were examined. Results: The patient was a Chinese girl born to nonconsanguineous parents. Since infancy she presented with recurrent oropharyngeal and perineal candidiasis that was refractory to antifungal treatment, and also had recurrent Salmonella gastroenteritis. At 5 years old, she developed granulomatous lymphadenitis caused by Mycobacterium fortuitum. At 14 months she developed type 1 diabetes mellitus and was treated with insulin. Exome sequencing identified a novel autosomal dominant loss-of-function E559K mutation in the linker domain of STAT1, which was confirmed by Sanger sequencing. The mutation impaired phosphorylation induced by both IFNγ and IFNα, leading to decreased expressions of interferon inducible target genes. STAT1 protein expression was not affected. Conclusions: In addition to mycobacterial infection, STAT1 loss-of-function mutation also predisposes to chronic mucocutaneous candidiasis, likely through aberrant regulation of IFN-mediated response. This extends the spectrum of clinical phenotype of STAT1 loss-of-function mutation. We also for the first time reported STAT1 mutation in the linker domain
Objective To investigate the effects of insulin-like growth factor 1 (IGF-1) on neonatal immunity... more Objective To investigate the effects of insulin-like growth factor 1 (IGF-1) on neonatal immunity. Methods Cord blood mononuclear cells (CBMC) from 10 normal, full-term infants, and 10 adults' peripheral blood mononuclear cells (PBMC, controls) were involved in this study. CBMC and PBMC were cultured in a serum and hormone-free medium. Cytokine activity was measured by ELISA. Results Compared with that of adults, the productions of IL-2, IL-4 and IFN-γ in PHA-stimulated CBMC were significantly decreased, and the productions of IL-10 and IL-12 in LPS-stimulated CBMC were also significantly reduced. IGF-1 alone could not induce IL-2, IL-4, IFN-y and IL-10 productions in CBMC or PBMC. However, it could induce a high level of IL-6 production and a low level of IL-12 production in CBMC or PBMC. IGF-1 significantly increased the productions of both IL-6 and IFN-γ in PHA-stimulated neonatal MNC. Moreover, it increased neonatal IFN-γproduction in PHA-stimulated CBMC to a level similar t...
Zhonghua er ke za zhi = Chinese journal of pediatrics, 2010
自2009年4月北美首次發現甲型H1N1流感病毒以來,該新型豬源病毒已播散至全球,引起21世紀首次流感大流行,對人類健康產生巨大威脅[1-2].與季節性流感不同,本次甲型H1N1流感大流行是由一... more 自2009年4月北美首次發現甲型H1N1流感病毒以來,該新型豬源病毒已播散至全球,引起21世紀首次流感大流行,對人類健康產生巨大威脅[1-2].與季節性流感不同,本次甲型H1N1流感大流行是由一種整合了古典豬流感、歐亞豬流感、禽流感和人季節性H3N2流感病毒基因的新型四源重組毒株引起.免疫系統包括先天性免疫和獲得性免疫系統,在構建了人體對流感病毒的防御體系的同時,也參與了流感病毒的致病機制.link_to_subscribed_fulltex
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