HIV-1–specific CD4+ T lymphocyte turnover and activation increase upon viral rebound
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
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
View: Text | PDF
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

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Effect of ART cessation on the physical numbers of Gag p24-specific CD4+...
Effect of ART cessation on the physical numbers of Gag p24-specific CD4+ T cells. PBMCs from 8 patients were stained with an HLA class II tetramer before, during, and after ART. (A) Longitudinal sampling of plasma viral load (pVL; top plot) and frequencies of p24.17-DR1 tetramer+ cells out of total CD4+ T cells (bottom plot). ART cessation is represented by the vertical dashed line, and the data are normalized for therapy cessation (defined as week 0). (B) The frequencies of p24.17-DR1 tetramer-positive CD4+ T cells are shown for 5 different clinical states: before antiretroviral therapy (preART), during the viral downslope while on ART (ART), once an undetectable viral load had been maintained for at least 1 month (pVL<50), upon viral rebound (Rebound), and during viral setpoint (Setpoint).