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|Título:||PD-1 and its ligand PD-L1 are progressively up-regulated on CD4 and CD8 T-cells in HIV-2 infection irrespective of the presence of viremia.|
Foxall, Russell B.
Baptista, António P.
Soares, Rui S.
Victorino, Rui M. M.
Sousa, Ana E.
|Editora:||Lippincott Williams & Wilkins|
|Citação:||AIDS 2012, Vol 26 No 9 p 1065–1071|
|Resumo:||Objective: Hyper-immune activation is a main determinant of HIV disease progression, potentially counter-acted by T-cell inhibitory pathways. Here we investigated, for the first time, inhibitory molecules in HIV-2 infection, a naturally occurring attenuated form of HIV disease, associated with reduced viremia and very slow rates of CD4 T-cell decline. Design: Programmed death (PD)-1/PD-L1, an important pathway in limiting immunopathology, and its possible relationship with T-cell immunoglobulin and mucin-domain containing molecule-3 (TIM-3), a recently identified inhibitory molecule, were studied in untreated HIV-2 and HIV-1 cohorts, matched for degree of CD4 T-cell depletion, and noninfected individuals. Methods: Flow cytometric analysis of T-cell expression of PD-1, PD-L1 and TIM-3, combined with markers of cell differentiation, activation, cycling and survival. Statistical analysis was performed using ANOVA, Mann–Whitney/Wilcoxon tests, Spearman's correlations, multiple linear regressions and canonical correlation analysis. Results: T-cell expression of PD-1 and PD-L1 was tightly associated and directly correlated with CD4 T-cell depletion and immune activation in HIV-2 infection. No such correlation was found for PD-L1 expression in HIV-1-positive patients. Central memory and intermediate memory cells, rather than terminally differentiated T-cells, expressed the highest levels of both PD-1 and PD-L1 molecules. Conversely, TIM-3 expression was independent of T-cell differentiation and dissociated from cell cycling, suggesting distinct induction mechanisms. Importantly, in contrast with HIV-1, no significant increases in TIM-3 expression were found in the HIV-2 cohort. Conclusions: Our data suggest that PD-1/PD-L1 molecules, rather than markers of T-cell exhaustion, may act as modulators of T-cell immune activation, contributing to the slower course of HIV-2 infection. These data have implications for the design of antiretroviral therapy-complementary immune-based strategies.|
|Descrição:||© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins|
|Versão do Editor:||The definitive version is available at http://journals.lww.com/pages/default.aspx|
|Aparece nas colecções:||FM - Artigos em Revistas Internacionais|
IMM - Artigos em Revistas Internacionais
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