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

Background. 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. Methods. We investigated the relationship between IL-10-...

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Bibliographic Details
Published in:Clinical infectious diseases 2012-01, Vol.54 (2), p.294-302
Main Authors: Naicker, Dshanta D., Wang, Bingxia, Losina, Elena, Zupkosky, Jennifer, Bryan, Susan, Reddy, Shabashini, Jaggernath, Manjeetha, Mokgoro, Mammekwa, Goulder, Philip J. R., Kaufmann, Daniel E., Ndung'u, Thumbi
Format: Article
Language:English
Subjects:
Adult
AIDS
CD4 Lymphocyte Count
Cytokines
Female
Genotype
Genotype & phenotype
Genotypes
HIV
HIV 1
HIV Infections - blood
HIV Infections - genetics
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
HIV/AIDS
Human immunodeficiency virus
Humans
Infections
Interferon-gamma - genetics
Interferon-gamma - immunology
Interleukin-10 - blood
Interleukin-10 - genetics
Interleukin-10 - immunology
Lymphocytes
Male
Medical genetics
Pathogenesis
Polymorphism
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Statistics, Nonparametric
T cell receptors
T lymphocytes
T-Lymphocytes, Cytotoxic - immunology
Viral Load
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Summary:Background. 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. Methods. 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. Results. 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). Conclusions. 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.
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/cir811