PMID- 22874514
OWN - NLM
STAT- MEDLINE
DCOM- 20130304
LR  - 20211021
IS  - 1473-5571 (Electronic)
IS  - 0269-9370 (Print)
IS  - 0269-9370 (Linking)
VI  - 26
IP  - 15
DP  - 2012 Sep 24
TI  - Impact of protective killer inhibitory receptor/human leukocyte antigen genotypes 
      on natural killer cell and T-cell function in HIV-1-infected controllers.
PG  - 1869-78
LID - 10.1097/QAD.0b013e32835861b0
AB  - 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. DESIGN: 
      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-alpha (IFNalpha) 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 IFNalpha 
      stimulation (P = 0.0201, n = 13). Interestingly, we observed a significant 
      inverse association between the IFNalpha 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). CONCLUSION: Together, these results suggest that heightened NK 
      responses can be evidenced independently of HIV-specific T-cell responses in 
      HIV-1-infected elite controllers.
FAU - Tomescu, Costin
AU  - Tomescu C
AD  - HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA 19104, 
      USA.
FAU - Duh, Fuh-Mei
AU  - Duh FM
FAU - Hoh, Rebecca
AU  - Hoh R
FAU - Viviani, Anne
AU  - Viviani A
FAU - Harvill, Kara
AU  - Harvill K
FAU - Martin, Maureen P
AU  - Martin MP
FAU - Carrington, Mary
AU  - Carrington M
FAU - Deeks, Steven G
AU  - Deeks SG
FAU - Montaner, Luis J
AU  - Montaner LJ
LA  - eng
GR  - P0 AI27763/AI/NIAID NIH HHS/United States
GR  - R21 AI078870/AI/NIAID NIH HHS/United States
GR  - R01 AI065279/AI/NIAID NIH HHS/United States
GR  - P01 AI076174/AI/NIAID NIH HHS/United States
GR  - K24AI069994/AI/NIAID NIH HHS/United States
GR  - P30 CA010815/CA/NCI NIH HHS/United States
GR  - K24 AI069994/AI/NIAID NIH HHS/United States
GR  - UL1 RR024131/RR/NCRR NIH HHS/United States
GR  - U01 AI065279/AI/NIAID NIH HHS/United States
GR  - R01 AI087145/AI/NIAID NIH HHS/United States
GR  - R01 AI073219/AI/NIAID NIH HHS/United States
GR  - R01 DA028775/DA/NIDA NIH HHS/United States
GR  - P30 AI027763/AI/NIAID NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - R24 AI067039/AI/NIAID NIH HHS/United States
GR  - AI 76174/AI/NIAID NIH HHS/United States
GR  - P30 CA10815/CA/NCI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - AIDS
JT  - AIDS (London, England)
JID - 8710219
RN  - 0 (KIR3DL1 protein, human)
RN  - 0 (RNA, Viral)
RN  - 0 (Receptors, KIR)
RN  - 0 (Receptors, KIR3DL1)
SB  - IM
MH  - Acquired Immunodeficiency Syndrome/*immunology/metabolism/physiopathology
MH  - Adaptive Immunity
MH  - Adult
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - California
MH  - Disease Progression
MH  - Female
MH  - Genotype
MH  - HIV Seropositivity/*immunology/metabolism/physiopathology
MH  - HIV-1/*immunology
MH  - Humans
MH  - Immunity, Innate
MH  - Killer Cells, Natural/*immunology
MH  - Male
MH  - RNA, Viral
MH  - Receptors, KIR/*immunology
MH  - Receptors, KIR3DL1/genetics/*immunology/metabolism
MH  - Virus Replication/immunology
PMC - PMC3810173
MID - NIHMS516519
EDAT- 2012/08/10 06:00
MHDA- 2013/03/05 06:00
PMCR- 2013/10/28
CRDT- 2012/08/10 06:00
PHST- 2012/08/10 06:00 [entrez]
PHST- 2012/08/10 06:00 [pubmed]
PHST- 2013/03/05 06:00 [medline]
PHST- 2013/10/28 00:00 [pmc-release]
AID - 10.1097/QAD.0b013e32835861b0 [doi]
PST - ppublish
SO  - AIDS. 2012 Sep 24;26(15):1869-78. doi: 10.1097/QAD.0b013e32835861b0.