Polyclonal anti-IgM antibodies were more effective than monoclonal antibodies in inducing dormanc... more Polyclonal anti-IgM antibodies were more effective than monoclonal antibodies in inducing dormancy in SCID mice bearing a murine B lymphoma (BCL1). Under saturating conditions, both polyclonal and monoclonal anti-Ig antibodies induced cell cycle arrest (CCA) in both BCL1 cells and human B lymphoma cells (Daudi) but polyclonal antibodies were far more effective at inducing apoptosis. A mixture of several monoclonal antibodies specific for noncrossreactive epitopes on C mu mimicked the effects of a polyclonal anti-mu. Hypercrosslinking mIgM by a polyclonal antibody against the primary monoclonal anti-mu markedly increased apoptosis and CCA. Hence, the extent of crosslinking of IgM and the resultant singnalling may be a major factor in inducing and maintaining dormancy and in determining whether lymphoma cells respond by apoptosis or CCA. In contrast to mIgM, another B cell receptor, CD40, which induces CCA when crosslinked did not induce apoptosis after hypercrosslinking. The results ...
The authors describe a set of seven peripheral T-cell lymphomas that lack detectable rearrangemen... more The authors describe a set of seven peripheral T-cell lymphomas that lack detectable rearrangements of T-cell receptor (TCR) genes. All cases showed antigenic profiles consistent with T-cell lymphoma, including expression of Leu-5 (CD2) antigen. However, few other T-lineage markers were found, and none of the cases tested (6 of 7) bound antibody recognizing the constant region of the beta TCR protein. Each case showed exclusively germline configurations of DNA for the beta TCR genes in Southern blot analyses with the use of several different combinations of restriction enzymes and DNA hybridization probes. One case contained clonal rearrangements of the gamma TCR gene and of the immunoglobulin heavy chain gene. Our results suggest that certain cases of peripheral T-cell lymphoma may lack rearrangements of TCR genes--particularly those cases expressing restricted numbers of T-lineage antigens. In view of these findings, failure to detect rearrangements of TCR genes by Southern blot a...
Adhesion to the vascular endothelium precedes or is a necessary prelude to leukocyte migration in... more Adhesion to the vascular endothelium precedes or is a necessary prelude to leukocyte migration into the underlying tissue. Constitutive lymphocyte trafficking through lymphoid organs is controlled by tissue-specific interactions between molecules expressed on the surface of the lymphocyte (homing receptors) and ligands (vascular addressins) expressed on endothelial cells (HEV) within lymphoid tissues. Preliminary evidence suggests that lymphocytes may employ related but distinct interactions in their entry into some chronic sites of inflammation. Other leukocytes, such as neutrophils and monocytes, express molecules related or identical to lymphocyte homing receptors, and these molecules are exquisitely regulated by chemotactic factors and appear to be involved in the homing of these cells to inflamed tissues. In addition, inflammation in vivo induces increased endothelial cell adhesiveness for leukocytes that undoubtedly plays a key role in regulating leukocyte extravasation. Tissu...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1998
CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-in... more CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-induced secretion of potent effector cytokines. The efficacy of these responses depends on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. Here, we provide evidence that heterogeneity in Ag triggering thresholds constitutes an additional critical determinant of memory T cell function. Using a novel assay that allows single-cell detection of Ag-specific T cell cytokine production, we demonstrate that CMV-specific CD4+ memory cells from human peripheral blood display pronounced differences in their costimulatory requirements for Ag-induced triggering of IFN-gamma and IL-2 secretion, ranging from cells that trigger with little costimulation (e.g., resting APC alone) to cells requiring potent costimulation through multiple pathways (resting APC plus multiple costimulatory mAbs, or activated APC). Thes...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1997
Although considerable attention has been paid to the development of cytokine synthesis heterogene... more Although considerable attention has been paid to the development of cytokine synthesis heterogeneity during memory T cell differentiation, little information is available on how this function is coregulated with homing receptor expression. The development of skin-homing, CD4+ memory T cells in the human provides an excellent model for such investigation, since 1) the skin supports both Th1- and Th2-predominant responses in different settings, and 2) the skin-homing capability of human memory T cells correlates with and appears to depend on expression of the skin-selective homing receptor cutaneous lymphocyte-associated Ag (CLA). In this study, we used multiparameter FACS analysis to examine expression of CLA vs IFN-gamma, IL-4, and IL-2 synthesis capabilities among fresh peripheral blood CD4+ memory T cells, and Th1 vs Th2 memory T cells generated in vitro from purified CD4+ naive precursors by cyclic activation in polarizing culture conditions. Among normal peripheral blood T cells...
The emergence of body cavity-based AIDS-related lymphoma as a new disease entity is a fascinating... more The emergence of body cavity-based AIDS-related lymphoma as a new disease entity is a fascinating story that is linked to the identification of a newly recognized human herpes virus, HHV-8. The current article in the American Journal of Clinical Pathology confirms the distinctive nature of this disease, 1 which to date has been reported almost exclusively in patients with HIV infection. 2,3 In addition, like Kaposi's sarcoma (KS) with which it is closely linked, it is seen primarily in homosexual males, but not in other HIV-positive risk groups. Body cavity-based lymphoma and KS both are associated with a novel human herpesvirus, Kaposi's sarcomaassociated herpesvirus (KSHV) or HHV-8. 4 Notably, the same virus has been found in KS lesions in patients with and without HIV infection. Therefore, the virus is not limited to the HIV-positive population.
The recent characterization of the cutaneous lymphocyte-associated antigen (CLA) as a skin-select... more The recent characterization of the cutaneous lymphocyte-associated antigen (CLA) as a skin-selective homing receptor for skin-associated memory T cells has suggested a possible mechanism for the tropism demonstrated by the neoplastic T cells in cutaneous T-cell lymphoma (CTCL). In this study, we used five parameter flow cytometry to evaluate expression of CLA and the peripheral lymph node homing receptor L-selectin on circulating T cells in a series of patients with CTCL. Because CTCL cells were previously shown to be CD7-, we looked at expression of these receptors on the CD7- T-cell subset as well as on total T cells. Our results indicate that CTCL patients have increased levels of both CLA+ and CD7- cells in their peripheral blood and that these abnormalities are not seen in patients with other cutaneous disorders. The levels of the CLA-bearing subset correlated with extent of cutaneous but not lymph node disease. By contrast, the CD7- L-selectin+ subset correlated with periphera...
Journal of immunology (Baltimore, Md. : 1950), 1993
Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation throug... more Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation through secondary lymphoid tissues, whereas memory/effector populations are composed of distinct subsets with differential, often tissue-selective migratory capability. In keeping with these observations, CD45RAhigh/ROlow "virgin" T cells in human peripheral blood uniformly express the peripheral lymph node homing receptor (HR) L-selectin, whereas among the CD45RAlow/ROhigh "memory/effector" subset, the expression of this HR is bimodal. To investigate the mechanisms responsible for the generation of memory/effector T cell subsets with differential homing potential, we developed a multiparameter flow cytometric technique that defines a common pathway of post-thymic T cell differentiation in secondary lymphoid tissues. Our analyses indicate that the virgin to memory T cell transition is characterized by a stepwise, unidirectional progression through distinct CD45RA+/RO+ inter...
The array of cytokines produced by T cells in effector sites is a primary means by which these ce... more The array of cytokines produced by T cells in effector sites is a primary means by which these cells mediate host defense. It is well recognized that cloned T cells are heterogeneous with regard to cytokine synthesis and, thus, in their ability to mediate specific immune responses, but the extent to which the patterns of cytokine secretion observed in cloned cells reflect actual populations of memory/effector T cells existing in vivo is largely unknown. Here, we report our findings using a multiparameter flow cytometric assay that allows simultaneous determination of an individual T-cell's ability to produce multiple cytokines and its phenotype after only short (4 to 8 hours) in vitro incubation with an activating stimulus and the secretion inhibitor Brefeldin A. This assay shows a rapid accumulation of interleukin-2 (IL-2), IL-4, and gamma-interferon (gamma-IFN) in the cytoplasm of CD4+ cells after stimulation with either accessory cell-independent (phorbol 12-myristate 13-acet...
Journal of immunology (Baltimore, Md. : 1950), 1995
The capacity of four subsets of CD4+ memory T cells, defined by expression of CD45RB and CD27, to... more The capacity of four subsets of CD4+ memory T cells, defined by expression of CD45RB and CD27, to provide help for B cells was examined. Larger amounts of Ig were induced by CD45RBdimCD27- cells compared with the CD45RBdimCD27+ population, whereas CD45RBbrightCD27+ or CD27- cells were poor inducers of Ig synthesis. Mitomycin C treatment, which prevents suppressive activity, markedly enhanced Ig production supported by each subset except for CD45RBbrightCD27- cells. Mitomycin C-treated CD45RBdim cells remained the most efficient inducers of Ig production, but no difference was detected between CD27+ and CD27- cells. The subsets also differed in their ability to proliferate and secrete cytokines, but these differences did not explain variations in the capacity to provide help for B cells. Both CD27- subsets exhibited decreased proliferation and uniquely secreted IL-4, with the CD45RBdimCD27- subset producing the greatest quantities of IL-4. No differences in IL-2 and IFN-gamma product...
Using an immunoperoxidase technique that identifies both surface and cytoplasmic antigen expressi... more Using an immunoperoxidase technique that identifies both surface and cytoplasmic antigen expression, the authors examined 28 benign reactive lymphorproliferative lesions and 55 T-lineage lymphomas for reactivity with CD3 (Leu-4; T-cell receptor-associated antigen) and beta F1 antibodies, the latter recognizing nonpolymorphic determinants on T-cell receptor beta chains. Consistent with previous observations that these two antigens are co-expressed on the vast majority of thymocytes, peripheral blood T cells and tonsillar T cells, all 28 reactive lymphoproliferations showed essentially identical patterns of CD3 and beta F1 expression. In contrast, only 29 of 55 T-lineage lymphomas displayed coexpression of these antigens. Among 33 peripheral T-cell lymphomas, 11 cases showed CD3/beta F1 discordance (7 CD3+/beta F1-; 4 CD3-/beta F1+), and 5 showed absence of both these antigens. Nine of 22 T-lymphoblastic lymphomas showed CD3/beta F1 discordance (all CD3+/beta F1-), and 1 case was CD3-...
Recent studies in both human and murine systems have demonstrated the existence of a second CD3-a... more Recent studies in both human and murine systems have demonstrated the existence of a second CD3-associated T cell receptor (the gamma delta-TCR) distinct from the alpha beta heterodimer associated with antigen recognition by classical T cells. Using a monoclonal antibody specific for the delta component of the human gamma delta-TCR, the expression of this antigen in both benign, reactive lymphoid tissues and T lineage lymphomas was studied with immunohistologic techniques. In the normal thymus, TCR-delta+ cells constituted less than 5% of the CD3+ thymocytes and were located primarily in the medulla or juxtamedullary cortex. Within the T zones of 16 histologically varied reactive peripheral lymphoid tissues, including four patients with marked predominantly paracortical hyperplasia, the authors identified from less than 1% to a maximum of 5% TCR-delta+ cells. While these results are consistent with the hypothesis that TCR-gamma delta+ cells comprise a small distinct subpopulation of...
It has been proposed that the skin is a functionally unique compartment of the immune system, alt... more It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CD8+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-delta-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion molecule high, CD45R low putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA-452 antigen is not a conventional activatio...
The thymus represents the major site of the production and generation of T cells expressing alpha... more The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.
Polyclonal anti-IgM antibodies were more effective than monoclonal antibodies in inducing dormanc... more Polyclonal anti-IgM antibodies were more effective than monoclonal antibodies in inducing dormancy in SCID mice bearing a murine B lymphoma (BCL1). Under saturating conditions, both polyclonal and monoclonal anti-Ig antibodies induced cell cycle arrest (CCA) in both BCL1 cells and human B lymphoma cells (Daudi) but polyclonal antibodies were far more effective at inducing apoptosis. A mixture of several monoclonal antibodies specific for noncrossreactive epitopes on C mu mimicked the effects of a polyclonal anti-mu. Hypercrosslinking mIgM by a polyclonal antibody against the primary monoclonal anti-mu markedly increased apoptosis and CCA. Hence, the extent of crosslinking of IgM and the resultant singnalling may be a major factor in inducing and maintaining dormancy and in determining whether lymphoma cells respond by apoptosis or CCA. In contrast to mIgM, another B cell receptor, CD40, which induces CCA when crosslinked did not induce apoptosis after hypercrosslinking. The results ...
The authors describe a set of seven peripheral T-cell lymphomas that lack detectable rearrangemen... more The authors describe a set of seven peripheral T-cell lymphomas that lack detectable rearrangements of T-cell receptor (TCR) genes. All cases showed antigenic profiles consistent with T-cell lymphoma, including expression of Leu-5 (CD2) antigen. However, few other T-lineage markers were found, and none of the cases tested (6 of 7) bound antibody recognizing the constant region of the beta TCR protein. Each case showed exclusively germline configurations of DNA for the beta TCR genes in Southern blot analyses with the use of several different combinations of restriction enzymes and DNA hybridization probes. One case contained clonal rearrangements of the gamma TCR gene and of the immunoglobulin heavy chain gene. Our results suggest that certain cases of peripheral T-cell lymphoma may lack rearrangements of TCR genes--particularly those cases expressing restricted numbers of T-lineage antigens. In view of these findings, failure to detect rearrangements of TCR genes by Southern blot a...
Adhesion to the vascular endothelium precedes or is a necessary prelude to leukocyte migration in... more Adhesion to the vascular endothelium precedes or is a necessary prelude to leukocyte migration into the underlying tissue. Constitutive lymphocyte trafficking through lymphoid organs is controlled by tissue-specific interactions between molecules expressed on the surface of the lymphocyte (homing receptors) and ligands (vascular addressins) expressed on endothelial cells (HEV) within lymphoid tissues. Preliminary evidence suggests that lymphocytes may employ related but distinct interactions in their entry into some chronic sites of inflammation. Other leukocytes, such as neutrophils and monocytes, express molecules related or identical to lymphocyte homing receptors, and these molecules are exquisitely regulated by chemotactic factors and appear to be involved in the homing of these cells to inflamed tissues. In addition, inflammation in vivo induces increased endothelial cell adhesiveness for leukocytes that undoubtedly plays a key role in regulating leukocyte extravasation. Tissu...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1998
CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-in... more CD4+ memory T cells coordinate immune responses against viruses and other pathogens via the Ag-induced secretion of potent effector cytokines. The efficacy of these responses depends on both the overall number of pathogen-specific memory T cells and the particular array of cytokines that these cells are programmed to secrete. Here, we provide evidence that heterogeneity in Ag triggering thresholds constitutes an additional critical determinant of memory T cell function. Using a novel assay that allows single-cell detection of Ag-specific T cell cytokine production, we demonstrate that CMV-specific CD4+ memory cells from human peripheral blood display pronounced differences in their costimulatory requirements for Ag-induced triggering of IFN-gamma and IL-2 secretion, ranging from cells that trigger with little costimulation (e.g., resting APC alone) to cells requiring potent costimulation through multiple pathways (resting APC plus multiple costimulatory mAbs, or activated APC). Thes...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 1997
Although considerable attention has been paid to the development of cytokine synthesis heterogene... more Although considerable attention has been paid to the development of cytokine synthesis heterogeneity during memory T cell differentiation, little information is available on how this function is coregulated with homing receptor expression. The development of skin-homing, CD4+ memory T cells in the human provides an excellent model for such investigation, since 1) the skin supports both Th1- and Th2-predominant responses in different settings, and 2) the skin-homing capability of human memory T cells correlates with and appears to depend on expression of the skin-selective homing receptor cutaneous lymphocyte-associated Ag (CLA). In this study, we used multiparameter FACS analysis to examine expression of CLA vs IFN-gamma, IL-4, and IL-2 synthesis capabilities among fresh peripheral blood CD4+ memory T cells, and Th1 vs Th2 memory T cells generated in vitro from purified CD4+ naive precursors by cyclic activation in polarizing culture conditions. Among normal peripheral blood T cells...
The emergence of body cavity-based AIDS-related lymphoma as a new disease entity is a fascinating... more The emergence of body cavity-based AIDS-related lymphoma as a new disease entity is a fascinating story that is linked to the identification of a newly recognized human herpes virus, HHV-8. The current article in the American Journal of Clinical Pathology confirms the distinctive nature of this disease, 1 which to date has been reported almost exclusively in patients with HIV infection. 2,3 In addition, like Kaposi's sarcoma (KS) with which it is closely linked, it is seen primarily in homosexual males, but not in other HIV-positive risk groups. Body cavity-based lymphoma and KS both are associated with a novel human herpesvirus, Kaposi's sarcomaassociated herpesvirus (KSHV) or HHV-8. 4 Notably, the same virus has been found in KS lesions in patients with and without HIV infection. Therefore, the virus is not limited to the HIV-positive population.
The recent characterization of the cutaneous lymphocyte-associated antigen (CLA) as a skin-select... more The recent characterization of the cutaneous lymphocyte-associated antigen (CLA) as a skin-selective homing receptor for skin-associated memory T cells has suggested a possible mechanism for the tropism demonstrated by the neoplastic T cells in cutaneous T-cell lymphoma (CTCL). In this study, we used five parameter flow cytometry to evaluate expression of CLA and the peripheral lymph node homing receptor L-selectin on circulating T cells in a series of patients with CTCL. Because CTCL cells were previously shown to be CD7-, we looked at expression of these receptors on the CD7- T-cell subset as well as on total T cells. Our results indicate that CTCL patients have increased levels of both CLA+ and CD7- cells in their peripheral blood and that these abnormalities are not seen in patients with other cutaneous disorders. The levels of the CLA-bearing subset correlated with extent of cutaneous but not lymph node disease. By contrast, the CD7- L-selectin+ subset correlated with periphera...
Journal of immunology (Baltimore, Md. : 1950), 1993
Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation throug... more Conventional virgin lymphocytes of a given class show relatively homogeneous recirculation through secondary lymphoid tissues, whereas memory/effector populations are composed of distinct subsets with differential, often tissue-selective migratory capability. In keeping with these observations, CD45RAhigh/ROlow "virgin" T cells in human peripheral blood uniformly express the peripheral lymph node homing receptor (HR) L-selectin, whereas among the CD45RAlow/ROhigh "memory/effector" subset, the expression of this HR is bimodal. To investigate the mechanisms responsible for the generation of memory/effector T cell subsets with differential homing potential, we developed a multiparameter flow cytometric technique that defines a common pathway of post-thymic T cell differentiation in secondary lymphoid tissues. Our analyses indicate that the virgin to memory T cell transition is characterized by a stepwise, unidirectional progression through distinct CD45RA+/RO+ inter...
The array of cytokines produced by T cells in effector sites is a primary means by which these ce... more The array of cytokines produced by T cells in effector sites is a primary means by which these cells mediate host defense. It is well recognized that cloned T cells are heterogeneous with regard to cytokine synthesis and, thus, in their ability to mediate specific immune responses, but the extent to which the patterns of cytokine secretion observed in cloned cells reflect actual populations of memory/effector T cells existing in vivo is largely unknown. Here, we report our findings using a multiparameter flow cytometric assay that allows simultaneous determination of an individual T-cell's ability to produce multiple cytokines and its phenotype after only short (4 to 8 hours) in vitro incubation with an activating stimulus and the secretion inhibitor Brefeldin A. This assay shows a rapid accumulation of interleukin-2 (IL-2), IL-4, and gamma-interferon (gamma-IFN) in the cytoplasm of CD4+ cells after stimulation with either accessory cell-independent (phorbol 12-myristate 13-acet...
Journal of immunology (Baltimore, Md. : 1950), 1995
The capacity of four subsets of CD4+ memory T cells, defined by expression of CD45RB and CD27, to... more The capacity of four subsets of CD4+ memory T cells, defined by expression of CD45RB and CD27, to provide help for B cells was examined. Larger amounts of Ig were induced by CD45RBdimCD27- cells compared with the CD45RBdimCD27+ population, whereas CD45RBbrightCD27+ or CD27- cells were poor inducers of Ig synthesis. Mitomycin C treatment, which prevents suppressive activity, markedly enhanced Ig production supported by each subset except for CD45RBbrightCD27- cells. Mitomycin C-treated CD45RBdim cells remained the most efficient inducers of Ig production, but no difference was detected between CD27+ and CD27- cells. The subsets also differed in their ability to proliferate and secrete cytokines, but these differences did not explain variations in the capacity to provide help for B cells. Both CD27- subsets exhibited decreased proliferation and uniquely secreted IL-4, with the CD45RBdimCD27- subset producing the greatest quantities of IL-4. No differences in IL-2 and IFN-gamma product...
Using an immunoperoxidase technique that identifies both surface and cytoplasmic antigen expressi... more Using an immunoperoxidase technique that identifies both surface and cytoplasmic antigen expression, the authors examined 28 benign reactive lymphorproliferative lesions and 55 T-lineage lymphomas for reactivity with CD3 (Leu-4; T-cell receptor-associated antigen) and beta F1 antibodies, the latter recognizing nonpolymorphic determinants on T-cell receptor beta chains. Consistent with previous observations that these two antigens are co-expressed on the vast majority of thymocytes, peripheral blood T cells and tonsillar T cells, all 28 reactive lymphoproliferations showed essentially identical patterns of CD3 and beta F1 expression. In contrast, only 29 of 55 T-lineage lymphomas displayed coexpression of these antigens. Among 33 peripheral T-cell lymphomas, 11 cases showed CD3/beta F1 discordance (7 CD3+/beta F1-; 4 CD3-/beta F1+), and 5 showed absence of both these antigens. Nine of 22 T-lymphoblastic lymphomas showed CD3/beta F1 discordance (all CD3+/beta F1-), and 1 case was CD3-...
Recent studies in both human and murine systems have demonstrated the existence of a second CD3-a... more Recent studies in both human and murine systems have demonstrated the existence of a second CD3-associated T cell receptor (the gamma delta-TCR) distinct from the alpha beta heterodimer associated with antigen recognition by classical T cells. Using a monoclonal antibody specific for the delta component of the human gamma delta-TCR, the expression of this antigen in both benign, reactive lymphoid tissues and T lineage lymphomas was studied with immunohistologic techniques. In the normal thymus, TCR-delta+ cells constituted less than 5% of the CD3+ thymocytes and were located primarily in the medulla or juxtamedullary cortex. Within the T zones of 16 histologically varied reactive peripheral lymphoid tissues, including four patients with marked predominantly paracortical hyperplasia, the authors identified from less than 1% to a maximum of 5% TCR-delta+ cells. While these results are consistent with the hypothesis that TCR-gamma delta+ cells comprise a small distinct subpopulation of...
It has been proposed that the skin is a functionally unique compartment of the immune system, alt... more It has been proposed that the skin is a functionally unique compartment of the immune system, although little direct evidence supporting this hypothesis has been presented. Here we show that lymphocyte populations at cutaneous sites can be differentiated from otherwise similar populations at noncutaneous sites by their preferential expression of an epitope defined by the MAb HECA-452. This MAb recognizes a predominantly 200-kd cell-surface glycoprotein present on about 16% of peripheral blood T cells, including both CD4+ and CD8+ T cells (17% and 11% HECA-452+, respectively), as well as TCR-delta-bearing T cells (32%+). Most thymocytes (99%) lacked HECA-452 antigen expression, and essentially all the HECA-452+ peripheral blood T cells were found in the adhesion molecule high, CD45R low putative memory cell subset, findings suggesting that HECA-452 expression develops peripherally as a consequence of antigenic stimulation. However, the HECA-452 antigen is not a conventional activatio...
The thymus represents the major site of the production and generation of T cells expressing alpha... more The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus can contribute to immune reconstitution following HAART.
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