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- Open Access
Association of interleukin-10 promoter genetic variants with T-cell and B-cell activation in HIV-1 infection
© Naicker et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Promoter Polymorphism
- Allelic Discrimination
- Immunoregulatory Cytokine
- TaqMan Allelic Discrimination
- Antibody Combination
Interleukin-10 (IL-10) is a potent immunoregulatory cytokine, with promoter polymorphisms that have previously been associated with HIV-1 susceptibility and pathogenesis. Association of IL-10 SNPs with markers of CD4, CD8 and B cell activation has not previously been investigated.
Two IL-10 polymorphisms were genotyped by TaqMan allelic discrimination and markers of activation of CD4, CD8 and B cells were measured in 63 individuals using flow cytometry. The following monoclonal antibody combinations were used: anti-CD3 Pac-blue, anti-CD38 PE-Cy7, anti-HLA-DR ACP-Cy7, anti-CD95 PE, anti-CD19 Alexa-700, anti-IgG PE-Cy5, anti-PD-1 APC, anti-Ki67 FITC, anti-CD4 Qdot605 and anti-CD8 Qdot655.
Previous studies on this cohort showed a significant association between -1082GG and higher median IL-10 expression, compared to the -1082AA/AG (p= 0.0006). The -592AA and -1082AA (both previously shown to be associated with low-IL-10 production) had significantly higher median expression of HLA-DR on CD4 and CD8 cells respectively, compared to the other genotypes (-592AA vs. -592CA p= 0.005, -592AA vs. -592CC p= 0.03 and -1082AA vs. -1082AG p= 0.02). The -592AA genotype also had a higher median expression of CD95 and PD-1 on CD4 cells (-592AA vs. -592CA p= 0.0227, -592AA vs. -592CC p= 0.0270 and -592AA vs. -592CA p= 0.01 respectively). The -592CC and -1082GG genotypes associated with higher median expression of IgG on the surface of B cells (-592CC vs. -592AA p= 0.0207 and -1082GG vs. -1082AG p= 0.0392, -1082GG vs. -1082AA p= 0.0051).
These data suggest that IL-10 polymorphisms that affect cytokine production and HIV pathogenesis may affect markers of immune activation and exhaustion in response to antigen, and suggest a beneficial role for IL-10 in chronic HIV infection. Further studies on association between IL-10 and the quality and magnitude of immune responses in HIV infection are needed.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.