title: Level of double negative T cells, which produce TGF-β and IL-10, predicts CD8 T-cell activation in primary HIV-1 infection.
abstract: OBJECTIVE
  Persistent immune activation plays a central role in the pathogenesis of HIV disease. Besides natural regulatory T cells (nTregs), 'double negative' T cells shown to exhibit regulatory properties could be involved in the control of harmful immune activation. The aim of this study was to analyze, in patients with primary HIV infection (PHI), the relationship between CD4(+)CD25(+)CD127(low)FoxP3(+) nTregs or CD3(+)CD4(-)CD8(-) double negative T cells and systemic immune activation.
  
  
  METHODS
  A prospective longitudinal study of patients with early PHI.
  
  
  METHODS
  Twenty-five patients were included. Relationships between frequency of Treg subsets and T-cell activation, assessed on fresh peripheral blood mononuclear cells, were analyzed using nonparametric tests. Cytokine production by double negative T cells was assessed following anti-CD3/anti-CD28 stimulation.
  
  
  RESULTS
  No relationship was found between T-cell activation and frequencies of nTregs. In contrast, a strong negative relationship was found at baseline between the proportion of double negative T cells and the proportion of activated CD8 T cells coexpressing CD38 and HLA-DR (P = 0.005) or expressing Ki-67 (P = 0.002). In addition, the frequency of double negative T cells at baseline negatively correlated with the frequency of HLA-DR(+)CD38(+)CD8(+) T cells at month 6, defining the immune activation set point (P = 0.031). High proportions of stimulated double negative T cells were found to produce the immunosuppressive cytokines transforming growth factor-β1 and/or IL-10.
  
  
  CONCLUSIONS
  The proportion of double negative T cells at baseline was found to be predictive of the immune activation set point. Our data strongly suggest that double negative T cells may control immune activation in PHI. This effect might be mediated through the production of TGF-β1/IL-10 known to downmodulate immune activation.
authors: Institut Pasteur, Régulation des infections rétrovirales, Département de Virologie, Paris, France.
authors: Gaël
authors: G
authors: Petitjean
authors: Mathieu F
authors: MF
authors: Chevalier
authors: Feriel
authors: F
authors: Tibaoui
authors: Céline
authors: C
authors: Didier
authors: Maria Elena
authors: ME
authors: Manea
authors: Anne-Sophie
authors: AS
authors: Liovat
authors: Pauline
authors: P
authors: Campa
authors: Michaela
authors: M
authors: Müller-Trutwin
authors: Pierre-Marie
authors: PM
authors: Girard
authors: Laurence
authors: L
authors: Meyer
authors: Françoise
authors: F
authors: Barré-Sinoussi
authors: Daniel
authors: D
authors: Scott-Algara
authors: Laurence
authors: L
authors: Weiss
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D005602:France; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000378:metabolism*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10