title: Phenotype alterations in regulatory T-cell subsets in primary HIV infection and identification of Tr1-like cells as the main interleukin 10-producing CD4+ T cells.
abstract: BACKGROUND
  Conventional regulatory T cells (Tregs) can suppress human immunodeficiency virus type 1 (HIV-1)-specific immune responses but cannot control immune activation in primary HIV infection. Here, we characterized Treg subsets, using recently defined phenotypic delineation, and analyzed the relative contribution of cell subsets to the production of immunosuppressive cytokines in primary HIV infection.
  
  
  METHODS
  In a longitudinal prospective study, ex vivo phenotyping of fresh peripheral blood mononuclear cells from patients with primary HIV infection was performed at baseline and month 6 of follow-up to characterize Treg subsets, immune activation, and cytokine production in isolated CD4(+) T cells.
  
  
  RESULTS
  The frequency of CD4(+)CD25(+)CD127(low) Tregs and the distribution between the naive, memory, and activated/memory Treg subsets was similar in patients and healthy donors. However, Tregs from patients with primary HIV infection showed peculiar phenotypic profiles, such as elevated FoxP3, ICOS, and CTLA-4 expression, with CTLA-4 expression strikingly increased in all Treg subsets both at baseline and month 6 of follow-up. The great majority of interleukin 10 (IL-10)-producing CD4(+) T cells were FoxP3(neg) (ie, Tr1-like cells). In contrast to conventional Tregs, Tr1-like cells were inversely correlated with immune activation and not associated with lower effector T-cell responses.
  
  
  CONCLUSIONS
  FoxP3(neg) Tr1-like cells-major contributors to IL-10 production-may have a beneficial role by controlling immune activation in early HIV infection.
authors.affiliation: Régulation des infections rétrovirales, Institut Pasteur Université Paris Diderot.
authors.forename: Mathieu F
authors.initials: MF
authors.lastname: Chevalier
authors.affiliation: Régulation des infections rétrovirales, Institut Pasteur.
authors.forename: Céline
authors.initials: C
authors.lastname: Didier
authors.affiliation: Régulation des infections rétrovirales, Institut Pasteur.
authors.forename: Gaël
authors.initials: G
authors.lastname: Petitjean
authors.affiliation: Hôpital Européen Georges Pompidou.
authors.forename: Marina
authors.initials: M
authors.lastname: Karmochkine
authors.affiliation: Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.affiliation: Régulation des infections rétrovirales, Institut Pasteur.
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.affiliation: Régulation des infections rétrovirales, Institut Pasteur.
authors.forename: Daniel
authors.initials: D
authors.lastname: Scott-Algara
authors.affiliation: Régulation des infections rétrovirales, Institut Pasteur Université Paris Descartes, Sorbonne Paris Cité Hôpital Européen Georges Pompidou.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
mesh_terms: D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D008137:Longitudinal Studies; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D016753:Interleukin-10
keywords: IL-10; Tr1; Treg subsets; activated Tregs; immune activation; memory Tregs; primary/acute HIV infection; regulatory T cells