Expansion of interferon‐γ‐secreting HIV‐specific T cells during successful antiretroviral therapy

• Published in: HIV medicine Vol. 14; no. 4; pp. 241 - 246
• Main Authors: Gasser, O, Brander, C, Wolbers, M, Brown, NV, Rauch, A, Günthard, HF, Battegay, M, Hess, C
• Format: Journal Article
• Language: English
• Published: England 01.04.2013
• Subjects: Adult; Anti-Retroviral Agents - therapeutic use; antiretroviral therapy; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cohort Studies; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunosorbent Assay - methods; Female; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1; HIV‐specific T cells; Human immunodeficiency virus; Humans; Interferon-gamma - immunology; Male; Middle Aged; Proteome; Retrospective Studies; Switzerland; T cell dynamics; Viral Load; Young Adult; Switzerland
• ISSN: 1464-2662; 1468-1293; 1468-1293
• DOI: 10.1111/j.1468-1293.2012.01040.x

Objectives Antiretroviral therapy (ART) suppresses HIV viraemia, thereby reducing the antigenic drive for T cells to proliferate. Accordingly, selected HIV‐specific T‐cell responses have been described to contract within weeks of ART initiation. Here, we sought to investigate whether these findings apply to the entire repertoire of HIV‐specific T cells. Methods Using interferon (IFN)‐γ enzyme linked immuno spot (ELISpot), we performed retrospective 2‐year proteome‐wide monitoring of HIV‐specific T cells in 17 individuals with undetectable viral loads during ART. The sample pool for each study subject consisted of one pre‐ART time‐point and at least two time‐points after initiation of therapy. Results Peripheral pools of HIV‐specific T cells decreased nonsignificantly within the first 2 years under ART in our cohort of patients, in terms of both breadth and magnitude. However, in most cases, the seeming decrease masked ongoing expansion of individual HIV‐specific T‐cell responses. We detected synchronous contraction and expansion of T‐cell responses – with different peptide specificities – in 12 out of 17 study participants during follow‐up. Importantly, the observed expansions and contractions of individual HIV‐specific T‐cell responses reached similar ranges, supporting the biological relevance of our findings. Conclusions We conclude that successful ART enables both contraction and expansion of HIV‐specific T‐cell responses. Our results should prompt a renewed interest in HIV‐specific T‐cell dynamics under ART, in particular to elucidate the mechanisms that uncouple, to some extent, particular HIV‐specific T‐cell responses from variations in circulating antigen load and functionally characterize expanding/contracting T‐cell populations beyond IFN‐γ secretion. Assuming that expanding HIV‐specific T‐cell responses under ART are protective and functional, harnessing those mechanisms may provide novel opportunities for assisting viral control in chronically infected individuals.