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doi: 10.1097/QAD.0000000000000315
Basic Science

HIV-1 Tat affects the programming and functionality of human CD8+ T cells by modulating the expression of T-box transcription factors

Sforza, Fabioa,*; Nicoli, Francescoa,*; Gallerani, Eleonoraa; Finessi, Valentinaa; Reali, Evab; Cafaro, Aurelioc; Caputo, Antonellad; Ensoli, Barbarac; Gavioli, Riccardoa

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Objective: HIV infection is characterized by several immune dysfunctions of both CD8+ and CD4+ T cells as hyperactivation, impairment of functionality and expansion of memory T cells. CD8+ T-cell dysfunctions have been associated with increased expression of T-bet, Eomesdermin and pro-inflammatory cytokines, and with down-regulation of CD127. The HIV-1 trans-activator of transcription (Tat) protein, which is released by infected cells and detected in tissues of HIV-positive individuals, is known to contribute to the dysregulation of CD4+ T cells; however, its effects on CD8+ T cells have not been investigated. Thus, in this study, we sought to address whether Tat may affect CD8+ T-cell functionality and programming.

Methods: CD8+ T cells were activated by T-cell receptor engagement in the presence or absence of Tat. Cytokine production, killing capacity, surface phenotype and expression of transcription factors important for T-cell programming were evaluated.

Results: Tat favors the secretion of interleukin-2, interferon-γ and granzyme B in CD8+ T cells. Behind this functional modulation we observed that Tat increases the expression of T-bet, Eomesdermin, Blimp-1, Bcl-6 and Bcl-2 in activated but not in unstimulated CD8+ T lymphocytes. This effect is associated with the down-regulation of CD127 and the up-regulation of CD27.

Conclusion: Tat deeply alters the programming and functionality of CD8+ T lymphocytes.

© 2014 Lippincott Williams & Wilkins, Inc.


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