Open AccessConferral of Enhanced Natural Killer Cell Function by KIR3DS1 in Early Human Immunodeficiency Virus Type 1 Infection
Author(s) -
Brian Long,
Lishomwa C. Ndhlovu,
Jorge R. Oksenberg,
Lewis L. Lanier,
Frederick M. Hecht,
Douglas F. Nixon,
Jason D. Barbour
Publication year - 2008
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02449-07
Subject(s) - biology , immunology , cd38 , receptor , microbiology and biotechnology , genetics , stem cell , cd34
A flurry of recent reports on the role of activating and inhibitory forms of the killer cell immunoglobulin-like receptors (KIR) in natural killer (NK) cell activity against human immunodeficiency virus type 1 (HIV-1) have yielded widely divergent results. The role of the activating NK receptor encoded by theKIR3DS1 allele and its putative ligands, members of the HLA class IBw4Ile80 cluster, in early HIV-1 disease is controversial. We selected 60 treatment-naïve adults for study from the OPTIONS cohort of individuals with early HIV-1 infection in San Francisco. We performed NK cell functional assays measuring gamma interferon (IFN-γ) and CD107a expression by NK cells in the unstimulated state and after stimulation by the major histocompatibility complex class I-deficient 721.221 B-lymphoblastoid cell line. In addition, we measured CD38 expression (a T-cell activation marker) on T and NK cells. Persons who have at least one copy of theKIR3DS1 gene had higher IFN-γ and CD107a expression in the unstimulated state compared to those who do not possess this gene. After stimulation, both groups experienced a large induction of IFN-γ and CD107a, withKIR3DS1 carriers achieving a greater amount of IFN-γ expression. Differences in effector activity correlating withKIR3DS1 were not attributable to joint carriage of HLABw4Ile80 andKIR3DS1 . We detected a partial but not complete dependence of KIR3DS1 on the members of B*58 supertype (B*57 and B*58) leading to higher NK cell function. PossessingKIR3DS1 was associated with lower expression of CD38 on both CD8+ T and NK cells and with a loss or weakening of the known strong associations between CD8+ T-cell expression of CD38 mean fluorescence intensity and the HIV-1 viral load. We observed that possessingKIR3DS1 was associated with higher NK cell effector functions in early HIV-1 disease, despite the absence of HLABw4Ile80 , a putative ligand of KIR3DS1. Carriage ofKIR3DS1 was associated with diminished CD8+ T-cell activation, as determined by expression of CD38, and a disruption of the traditional relationship between viral load and activation in HIV-1 disease, which may lead to better clinical outcomes for these individuals.