Receptor-Ligand Requirements for Increased NK Cell Polyfunctional Potential in Slow Progressors Infected with HIV-1 Coexpressing KIR3DL1*h/*y and HLA-B*57
Por:
Kamya, P, Boulet, S, Tsoukas, CM, Routy, JP, Thomas, R, Cote, P, Boulassel, MR, Baril, JG, Kovacs, C, Migueles, SA, Connors, M, Suscovich, TJ, Brander, C, Tremblay, CL and Bernard, N
Publicada:
1 jun 2011
Resumen:
Carriage of the natural killer (NK) receptor genotype KIR3DL1*h/*y with its HLA-B*57 ligand (*h/*y+B*57) is associated with slow time to AIDS and low viral load (VL). To provide a functional basis for these epidemiological observations, we assessed whether HIV-1-infected slow progressors (SP) carrying the *h/*y+B*57 compound genotype would have increased NK cell polyfunctional potential in comparison to SP with other killer immunoglobulin-like receptor (KIR)/HLA compound genotypes and whether this enhanced poly-functionality was dependent upon the coexpression of both KIR3DL1*h/*y and HLA-B*57. The functional potential of NK cells was investigated by stimulating peripheral blood mononuclear cells with HLA-devoid targets or single HLA transfectants. Multiparametric flow cytometry was used to detect NK cells with seven functional profiles representing all permutations of CD107a expression and gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) secretion. NK cells from individuals carrying KIR3DL1 receptor-HLA-Bw4 ligand pairs had greater trifunctional responses than those from KIR3DL1 homozygotes (hmz), who were Bw6 homozygotes. NK cells from subjects carrying the *h/*y+B*57 genotypes exhibited the highest trifunctional potential, and this was dependent on cocarriage of the NK receptor and its ligand. Trifunctional cells secreted more of each function tested on a per-cell basis than each corresponding monofunctional NK subset. Although VL influenced NK functionality, individuals with defined KIR/HLA genotypes exhibited differences in NK cell polyfunctionality that could not be accounted for by VL alone. The protective effect of HLA-B*57 on slow progression to AIDS and low VL may be mediated through its interaction with KIR3DL1 alleles to educate NK cells for potent activity upon stimulation.
Filiaciones:
Kamya, P:
McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada
McGill Univ, Div Expt Med, Montreal, PQ H3G 1A4, Canada
Boulet, S:
McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada
Tsoukas, CM:
McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada
McGill Univ, Div Expt Med, Montreal, PQ H3G 1A4, Canada
McGill Univ, Ctr Hlth, Div Clin Immunol & Allergy, Montreal, PQ H3G 1A4, Canada
Routy, JP:
McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada
McGill Univ, Ctr Hlth, Royal Victoria Hosp, Immunodeficiency Serv, Montreal, PQ H3G 1A4, Canada
McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Hematol, Montreal, PQ H3G 1A4, Canada
Thomas, R:
Clin Actuel, Montreal, PQ, Canada
Cote, P:
Clin Quartier Latin, Montreal, PQ, Canada
Boulassel, MR:
McGill Univ, Ctr Hlth, Royal Victoria Hosp, Immunodeficiency Serv, Montreal, PQ H3G 1A4, Canada
McGill Univ, Ctr Hlth, Royal Victoria Hosp, Div Hematol, Montreal, PQ H3G 1A4, Canada
Baril, JG:
Clin Quartier Latin, Montreal, PQ, Canada
Kovacs, C:
Maple Leaf Med Clin, Toronto, ON, Canada
Migueles, SA:
NIAID, NIH, Bethesda, MD 20892 USA
Connors, M:
NIAID, NIH, Bethesda, MD 20892 USA
Suscovich, TJ:
Benaroya Res Inst, Seattle, WA USA
:
Hosp Badalona Germans Trias & Pujol, IrsiCaixa AIDS Res Inst, Barcelona, Spain
ICREA, Barcelona, Spain
Tremblay, CL:
Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ, Canada
Bernard, N:
McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada
McGill Univ, Div Expt Med, Montreal, PQ H3G 1A4, Canada
McGill Univ, Ctr Hlth, Div Clin Immunol & Allergy, Montreal, PQ H3G 1A4, Canada
Green Published
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