title: Expansion of interferon-γ-secreting HIV-specific T cells during successful antiretroviral therapy.
abstract: OBJECTIVE
  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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Gasser
authors.forename: C
authors.initials: C
authors.lastname: Brander
authors.forename: M
authors.initials: M
authors.lastname: Wolbers
authors.forename: N V
authors.initials: NV
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Rauch
authors.forename: H F
authors.initials: HF
authors.lastname: Günthard
authors.forename: M
authors.initials: M
authors.lastname: Battegay
authors.forename: C
authors.initials: C
authors.lastname: Hess
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020543:Proteome; D012189:Retrospective Studies; D013557:Switzerland; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D020543:Proteome; D007371:Interferon-gamma