Immunodominant HIV-1-specific HLA-B- and HLA-C-restricted CD8+ T cells do not differ in polyfunctionality

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• 作者：Nompumelelo Mkhwanazi ; Christina F. Thobakgale ; Mary van der Stok ; Shabashini Reddy ; Zenele Mncube ; Fundisiwe Chonco ; Bruce D. Walker ; Marcus Altfeld ; Philip J.R. Goulder ; Thumbi Ndung'u
• 关键词：HLA-B*57/5801 ; HLA-C ; HIV-1 chronic infection ; CD8+ T cells ; Polyfunctionality
• 刊名：Virology
• 出版年：2010
• 出版时间：30 September 2010
• 年：2010
• 卷：405
• 期：2
• 页码：483-491
• 全文大小：845 K

文摘

HIV-1 specific HLA-B-restricted CD8+ T cell responses differ from HLA-C-restricted responses in antiviral effectiveness. To investigate possible reasons for these differences, we characterized the frequency and polyfunctionality of immmunodominant HLA-B*57/B5801- and HLA-Cw*07-restricted CD8+ T cells occurring concurrently in nine study subjects assessing IFN-γ, TNF-α, IL-2, MIP-1β, and CD107a by flow cytometry and analyzed sequence variation in targeted epitopes. HLA-B*57/5801 and HLA-Cw*07 restricted CD8+ T cells did not differ significantly in polyfunctionality (p = 0.84). Possession of three or more functions correlated positively with CD4+ T cell counts (r = 0.85; p = 0.006) and monofunctional CD8+ T cells inversely correlated with CD4 cell counts (r = −0.79; p = 0.05). There were no differences in polyfunctionality of CD8+ T cells specific to wildtype versus mutated epitopes. These results suggest that loss of polyfunctionality and increase in monofunctional HIV-1-specific CD8+ T cells are associated with disease progression independent of restricting HLA allele. Furthermore, sequence variation does not appear to significantly impact CD8+ T cell polyfunctionality in chronic HIV-1 infection.