T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+ T Cells in HIV Infection

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CD8+ T cells display numerous traits of severe dysfunction in both treated and untreated HIV infection. Previous studies have demonstrated that HIV-specific CD8+ T cells in most individuals possess poor polyfunctionality, and an immature/skewed maturation phenotype. However, it remains unclear which transcriptional programming governs the regulation of CD8+ T cell differentiation and exhaustion in HIV infection. T-bet and Eomes represent two key transcription factors for CD8+ T cell differentiation and function, but surprisingly little is known about their influence of effector immunity following chronic viral infections in humans. In this study, we demonstrate that HIV-specific CD8+ T cells possess highly elevated levels of Eomes, but low T-bet expression. This differential relationship is linked to the up-regulation of several inhibitory receptors, impaired functional characteristics and a transitional memory differentiation phenotype for virus-specific CD8+ T cells. Importantly, these characteristics of HIV-specific CD8+ T cells remained stable despite suppressive ART for many years. These results implicate that reinvigoration of these cells might fail to elicit efficient responses to eradicate the viral reservoir.

Vyšlo v časopise: T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+ T Cells in HIV Infection. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004251
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004251

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