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Expansion of interferon‐γ‐secreting HIV ‐specific T cells during successful antiretroviral therapy
Author(s) -
Gasser O,
Brander C,
Wolbers M,
Brown NV,
Rauch A,
Günthard HF,
Battegay M,
Hess C
Publication year - 2013
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2012.01040.x
Subject(s) - medicine , antiretroviral therapy , immunology , viral load , human immunodeficiency virus (hiv) , t cell , cell , interferon , cd4 t cell , biology , immune system , genetics
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 ( ELIS pot), 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.