Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science, c2005-

Immunity, Cellular*/drug effects; Antibodies, Viral/*analysis ; CD8-Positive T-Lymphocytes/*immunology ; HIV/*immunology ; HIV Infections/*immunology ; Receptors, Antigen, T-Cell/*biosynthesis ; Viremia/*immunology; Anti-Retroviral Agents/therapeutic use ; Antibody Affinity ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/metabolism ; Chronic Disease ; Cohort Studies ; Cross-Sectional Studies ; Cyclosporine/therapeutic use ; Disease Progression ; Epitope Mapping ; HIV/drug effects ; HIV/growth & development ; HIV/isolation & purification ; HIV Infections/blood ; HIV Infections/drug therapy ; HIV Infections/virology ; Humans ; Immunosuppressive Agents/therapeutic use ; Longitudinal Studies ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/metabolism ; Up-Regulation/drug effects ; Viremia/blood ; Viremia/drug therapy ; Viremia/virology ; Virus Replication/drug effects

The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses.

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0 (Anti-Retroviral Agents)
0 (Antibodies, Viral)
0 (Immunosuppressive Agents)
0 (Receptors, Antigen, T-Cell)
83HN0GTJ6D (Cyclosporine)

Date Created: 20130716 Date Completed: 20140218 Latest Revision: 20211021

20221213

PMC3701695

10.1371/journal.ppat.1003423

23853580