title: Impact of protective killer inhibitory receptor/human leukocyte antigen genotypes on natural killer cell and T-cell function in HIV-1-infected controllers.
abstract: OBJECTIVE
  Both protective T-cell genotypes and natural killer (NK) cell genotypes have been associated with delayed progression to AIDS and shown to be co-inherited in HIV-1-infected individuals who limit viral replication in absence of antiretroviral therapy ('controllers'). However, a comparative analysis of the genotype and function of the innate and adaptive immune compartments in HIV-1-infected controller individuals has been understudied to date.
  
  
  METHODS
  Here, we simultaneously tested NK and T-cell function in controllers to investigate the mechanism(s) that might account for host immune control over viral replication.
  
  
  METHODS
  We measured CD8 T-cell responses against HIV-1 utilizing overlapping 15-mer peptides spanning the HIV-1 consensus clade B Gag protein and tested NK cell degranulation and cytokine secretion against tumor target cells following interferon-α (IFNα) stimulation.
  
  
  RESULTS
  Among a cohort of 37 controllers, the presence of protective major histocompatibility complex class I human leukocyte antigen (HLA) alleles (such as HLA-B*57) was not correlated with HIV-specific CD8 responses. In contrast, the inheritance of a protective killer inhibitory receptor KIR3DL1*h/*y receptor genotype along with the corresponding HLA-Bw4*80I ligand was associated with significantly heightened target cell-induced NK degranulation and cytokine secretion following IFNα stimulation (P = 0.0201, n = 13). Interestingly, we observed a significant inverse association between the IFNα stimulated NK response to K562 cells and the HIV-specific CD8 T-cell response to Gag among elite controllers (rho = -0.8321, P = 0.0010, n = 12).
  
  
  CONCLUSIONS
  Together, these results suggest that heightened NK responses can be evidenced independently of HIV-specific T-cell responses in HIV-1-infected elite controllers.
authors.affiliation: HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Costin
authors.initials: C
authors.lastname: Tomescu
authors.forename: Fuh-Mei
authors.initials: FM
authors.lastname: Duh
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: Anne
authors.initials: A
authors.lastname: Viviani
authors.forename: Kara
authors.initials: K
authors.lastname: Harvill
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D056704:Adaptive Immunity; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002140:California; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006679:HIV Seropositivity / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D012367:RNA, Viral; D054340:Receptors, KIR / Q000276:immunology*; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication / Q000276:immunology
chemical_list: C515083:KIR3DL1 protein, human; D012367:RNA, Viral; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1