Titre
Association of IL-10-promoter genetic variants with the rate of CD4 T-cell loss, IL-10 plasma levels, and breadth of cytotoxic T-cell lymphocyte response during chronic HIV-1 infection.
Type
article
Institution
Externe
Périodique
Auteur(s)
Naicker, D.D.
Auteure/Auteur
Wang, B.
Auteure/Auteur
Losina, E.
Auteure/Auteur
Zupkosky, J.
Auteure/Auteur
Bryan, S.
Auteure/Auteur
Reddy, S.
Auteure/Auteur
Jaggernath, M.
Auteure/Auteur
Mokgoro, M.
Auteure/Auteur
Goulder, P.J.
Auteure/Auteur
Kaufmann, D.E.
Auteure/Auteur
Ndung'u, T.
Auteure/Auteur
Liens vers les personnes
ISSN
1537-6591
Statut éditorial
Publié
Date de publication
2012-01-15
Volume
54
Numéro
2
Première page
294
Dernière page/numéro d’article
302
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Interleukin-10 (IL-10) is a potent immunoregulatory cytokine. IL-10-promoter polymorphisms have been shown to affect human immunodeficiency virus type 1 (HIV-1) clinical outcomes but the underlying mechanisms are poorly understood.
We investigated the relationship between IL-10-promoter variants, plasma cytokine levels, immune responses and markers of disease outcome in antiretroviral-naïve HIV-1 chronically infected individuals from South Africa. Two IL-10-promoter single nucleotide polymorphisms (SNPs) were genotyped in 451 participants. Baseline plasma levels of select cytokines were measured for 112 individuals. Viral load, CD4(+) T-cell counts and HIV-1-specific interferon-gamma CD8(+) T-cell immune responses were measured at baseline. CD4(+) T-cell counts were measured longitudinally and rates of CD4(+) T-cell decline computed for 300 study subjects.
The minor IL-10-1082G and -592A variants occurred at frequencies of 0.31 and 0.34, respectively. The -592AA genotype associated significantly with attenuated loss of CD4(+) T cells (P = .0496). Individuals possessing -1082GG had significantly higher IL-10 levels compared to -1082AA/AG (P = .0006). The -592AA genotype was associated with greater breadth of virus-specific CD8(+) T-cell responses compared to CC and CA (P = .002 and .004 respectively).
IL-10-promoter variants may influence the rate of HIV-1 disease progression by regulating IL-10 levels and the breadth of CD8(+) T-cell immune responses.
We investigated the relationship between IL-10-promoter variants, plasma cytokine levels, immune responses and markers of disease outcome in antiretroviral-naïve HIV-1 chronically infected individuals from South Africa. Two IL-10-promoter single nucleotide polymorphisms (SNPs) were genotyped in 451 participants. Baseline plasma levels of select cytokines were measured for 112 individuals. Viral load, CD4(+) T-cell counts and HIV-1-specific interferon-gamma CD8(+) T-cell immune responses were measured at baseline. CD4(+) T-cell counts were measured longitudinally and rates of CD4(+) T-cell decline computed for 300 study subjects.
The minor IL-10-1082G and -592A variants occurred at frequencies of 0.31 and 0.34, respectively. The -592AA genotype associated significantly with attenuated loss of CD4(+) T cells (P = .0496). Individuals possessing -1082GG had significantly higher IL-10 levels compared to -1082AA/AG (P = .0006). The -592AA genotype was associated with greater breadth of virus-specific CD8(+) T-cell responses compared to CC and CA (P = .002 and .004 respectively).
IL-10-promoter variants may influence the rate of HIV-1 disease progression by regulating IL-10 levels and the breadth of CD8(+) T-cell immune responses.
Sujets
PID Serval
serval:BIB_9FD991AEAD9E
PMID
URL éditeur
Date de création
2023-05-09T12:00:06.039Z
Date de création dans IRIS
2025-05-21T02:19:03Z