title: Immune responses driven by protective human leukocyte antigen alleles from long-term nonprogressors are associated with low HIV reservoir in central memory CD4 T cells.
abstract: BACKGROUND
  The stable immune control of human immunodeficiency virus (HIV) in long-term nonprogressors (LTNPs) with protective human leukocyte antigen (HLA) alleles raises the question of whether and how these alleles influence the immune distribution of the HIV reservoirs.
  
  
  METHODS
  Cell-associated HIV-DNA levels were quantified in blood sorted resting CD4 T-cell subsets from 8 LTNPs with and 10 without HLA-B*27 or HLA-B*57 alleles (HLA-B27/B57).
  
  
  RESULTS
  A remarkably lower infection level of central memory CD4 T cells (T(CM)) was an exclusive feature that distinguished the HLA-B27/B57 HIV reservoirs from the other ones. In LTNPs, T(CM) protection was correlated with preservation of T(CM) counts, which correlated positively with the magnitude of HIV Gag-specific CD8 T cells. In HLA-B27/B57 LTNPs, a lower activation level of their memory CD4 T cells was associated with lower amounts of cell HIV-DNA in each resting memory CD4 subset and were also associated with higher ratios of HIV Gag-specific CD8 T cells per infected resting CD4 T cell (effector/target [E/T]). As a result, HLA-B27/B57 E/T ratios were negatively correlated with the contribution of memory CD4 T-cell subsets to the total HIV reservoirs.
  
  
  CONCLUSIONS
  The potent antiviral immunity governed by the protective HLA-B27/B57 alleles, by limiting T(CM) infection and pool exhaustion, are associated with a reduced T(CM) contribution to the HIV reservoir.
authors.affiliation: Immunity and Infection Laboratory, Pierre and Marie Curie University, INSERM UMRS 945, Pitie-Salpetriere Hospital, Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Descours
authors.forename: Veronique
authors.initials: V
authors.lastname: Avettand-Fenoel
authors.forename: Catherine
authors.initials: C
authors.lastname: Blanc
authors.forename: Assia
authors.initials: A
authors.lastname: Samri
authors.forename: Adeline
authors.initials: A
authors.lastname: Mélard
authors.forename: Virginie
authors.initials: V
authors.lastname: Supervie
authors.forename: Ioannis
authors.initials: I
authors.lastname: Theodorou
authors.forename: Guislaine
authors.initials: G
authors.lastname: Carcelain
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
authors.forename: Brigitte
authors.initials: B
authors.lastname: Autran
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000302:isolation & purification; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D020276:HIV Long-Term Survivors; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D011533:Proviruses / Q000302:isolation & purification; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D015235:HLA-B Antigens