HIV-1–specific CD4+ T lymphocyte turnover and activation increase upon viral rebound
Thomas J. Scriba, … , Michaela Lucas, Rodney E. Phillips
Thomas J. Scriba, … , Michaela Lucas, Rodney E. Phillips
Published February 1, 2005
Citation Information: J Clin Invest. 2005;115(2):443-450. https://doi.org/10.1172/JCI23084.
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Article AIDS/HIV

HIV-1–specific CD4+ T lymphocyte turnover and activation increase upon viral rebound

Abstract

HIV-specific CD4+ T helper lymphocytes are preferred targets for infection. Although complete interruption of combination antiretroviral therapy (ART) can form part of therapeutic manipulations, there is grave concern that the resumption of viral replication might destroy, perhaps irreversibly, these T helper populations. High viremia blocks the proliferation capacity of HIV-specific helper cells. However, cytokine production assays imply that some antigen-specific effector function is retained. Despite this careful work, it remains unclear whether the return of HIV-1 replication physically destroys HIV-1–specific T helper cells in the peripheral blood. Difficulties in producing stable peptide-MHC class II complexes and the very low frequencies of antigen-specific CD4+ T cells have delayed the application of this powerful technique. Here we employ HLA class II tetramers and validate a sensitive, quantitative cell-enrichment technique to detect HIV-1 T helper cells. We studied patients with early-stage HIV infection who were given a short, fixed course of ART as part of a clinical study. We did not find significant deletion of these cells from the peripheral circulation when ART was stopped and unfettered HIV replication returned. The turnover of these virus-specific cells increased and they adopted an effector phenotype when viremia returned.

Authors

Thomas J. Scriba, Hua-Tang Zhang, Helen L. Brown, Annette Oxenius, Norbert Tamm, Sarah Fidler, Julie Fox, Jonathan N. Weber, Paul Klenerman, Cheryl L. Day, Michaela Lucas, Rodney E. Phillips

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Phenotypic analysis of HIV-specific memory CD4+ T cells using HLA class ...
Phenotypic analysis of HIV-specific memory CD4+ T cells using HLA class II tetramers. (A) Representative phenotypic staining with anti-CD27, anti-CD28, or anti-CD62L antibodies from subject Ox73. FACS plots are gated on CD4+ T lymphocytes, and the percentage of tetramer+ CD4+ T cells expressing the respective phenotypic marker is indicated in the upper right quadrant of each plot. (B) Phenotypic profile of HIV-specific CD4+ T cells in 9 viremic individuals. Each bar represents the mean percentage of tetramer+ CD4+ cells that express the indicated surface marker. Error bars represent SEM. (C) CCR7 expression on CD4+ T cell subsets in viremic HIV infection. CD45RA+ and CD45RA– CD4+ cells were gated on to distinguish between the naive and memory subsets, respectively. (D) The HIV-1–specific, tetramer+ CD4+ T cell subset was significantly more activated than the memory CD4+ T cell population. CD38 expression was measured in 9 viremic patients. Cells that fell into the CD45RA–CD4+ or tetramer+ CD4+ gates were analyzed. The means are represented by horizontal lines and the statistical differences between them were calculated with a paired Student’s t test.