Patricia Price

Curtin University, School of Biomedical Sciences, Faculty Member

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HIV patients stable on ART retain evidence of a high CMV load but changes to Natural Killer cell phenotypes reflect both HIV and CMV

AIDS research and therapy, 2015

Whilst ART corrects many effects of HIV disease, T cell populations retain features of accelerate... more Whilst ART corrects many effects of HIV disease, T cell populations retain features of accelerated immunological aging. Here we analyse phenotypic changes to natural killer (NK) cells in HIV patients who began ART with <200 CD4 T-cells/µl and maintained virological control for 12-17 years, compared with CMV seropositive and seronegative healthy control donors. Humoral responses to CMV antigens (lysate, gB, IE-1) remain elevated in the patients (P < 0.0001) despite the long duration of ART. Patient's NK cells responded poorly to K562 cells when assessed by CD107a and IFNγ, but this could not be attributed to CMV as responses were low in CMV-seronegative controls. Moreover HIV (and not CMV) increased expression of CD57 on CD56(lo) cells. Comparisons with published studies suggest that CMV accelerates age-related increases in CD57 expression but levels plateau by 60-70 years of age, so the effect of CMV disappears. In HIV patients the plateau is higher and perhaps reached soo...

Effect of a Retroviral Immunodeficiency Syndrome on Resistance to MCMV: A Role for Natural Killer Cells

Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Nov 1, 1995

Mice exhibiting T cell immunodeficiency and lymphadenopathy induced by LP-BM5 MuLV (MAIDS) were a... more Mice exhibiting T cell immunodeficiency and lymphadenopathy induced by LP-BM5 MuLV (MAIDS) were assessed for their ability to control murine cytomegalovirus (MCMV) infection. Elevated replication of MCMV was observed in spleens 4-6 days after MCMV infection. Production of interferon alpha/beta in response to MCMV was abrogated by MAIDS and natural killer (NK) cell activity, assessed by lysis of YAC-1 target cells, was correspondingly depressed on Day 1. However, this was elevated at later times. As previous studies attribute early control of MCMV in C57BL mice with splenic NK1.1 cells, we confirmed that YAC-1 lysis declines and MCMV titres are elevated in M- mice given antibodies to NK1.1 or asialo GM1. However, M+ mice were less severely affected by these regimes. Hence M+ mice may acquire cells that do not express NK1.1 or asialo GM1, but are able to lyse YAC-1 target cells and partially control MCMV replication. MCMV was essentially cleared from the spleens and livers of M+ and M- mice by Day 11, but in the salivary gland MCMV replication was enhanced by MAIDS 11-30 days postinfection. The role of CD4 T cells in this phenomenon is being investigated. Since patients with acquired immunodeficiency syndrome exhibit suppressed T and NK cell activity and experience severe cytomegalovirus disease, the model warrants further study.

Patricia Price

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