Objective: HIV infection is characterized by several immune dysfunctions, such as chronic activation of the immune system, premature aging and loss of CD4 + T cells, in particular within the naïve compartment. The Tat protein of HIV is released extracellularly and enters neighboring cells affecting their functionality, for instance impacting on CD8 + T-cell programs and activity. As the presence and/or induction of anti-Tat immune responses is associated with reduced T-cell dysfunction and CD4 + T-cell loss, we investigated whether Tat impacts human resting or activated CD4 + T cells. Methods: Purified CD4 + T cells were activated by T cell receptor engagement in the presence or absence of Tat. Cytokine production, surface phenotype and expression of transcription factors important for T-cell programing were measured. Purified naïve CD4 + T cells were cultured in nonpolarizing conditions in the presence or absence of Tat and their proliferation and differentiation was evaluated. Results: Tat favors the secretion of IL2, IFNγ and TNFα in CD4 + T cells, as well as the upregulation of T-bet and Eomes expression. Naïve CD4 + T cells cultured in the presence of Tat showed enhanced expansion and differentiation toward memory phenotype, showing in particular recruitment into the effector memory T-cell pool. Conclusion: Tat affects the programing and functionality of CD4 + T lymphocytes favoring the differentiation of naïve CD4 + T cells.

The HIV-1 Tat protein affects human CD4+ T cell programming and activation, and favors the differentiation of naïve CD4+ T cells

Nicoli, Francesco
Primo
;
Gallerani, Eleonora
Secondo
;
Sforza, Fabio;Finessi, Valentina;Ensoli, Barbara;Caputo, Antonella
Penultimo
;
Gavioli, Riccardo
Ultimo
2018

Abstract

Objective: HIV infection is characterized by several immune dysfunctions, such as chronic activation of the immune system, premature aging and loss of CD4 + T cells, in particular within the naïve compartment. The Tat protein of HIV is released extracellularly and enters neighboring cells affecting their functionality, for instance impacting on CD8 + T-cell programs and activity. As the presence and/or induction of anti-Tat immune responses is associated with reduced T-cell dysfunction and CD4 + T-cell loss, we investigated whether Tat impacts human resting or activated CD4 + T cells. Methods: Purified CD4 + T cells were activated by T cell receptor engagement in the presence or absence of Tat. Cytokine production, surface phenotype and expression of transcription factors important for T-cell programing were measured. Purified naïve CD4 + T cells were cultured in nonpolarizing conditions in the presence or absence of Tat and their proliferation and differentiation was evaluated. Results: Tat favors the secretion of IL2, IFNγ and TNFα in CD4 + T cells, as well as the upregulation of T-bet and Eomes expression. Naïve CD4 + T cells cultured in the presence of Tat showed enhanced expansion and differentiation toward memory phenotype, showing in particular recruitment into the effector memory T-cell pool. Conclusion: Tat affects the programing and functionality of CD4 + T lymphocytes favoring the differentiation of naïve CD4 + T cells.
Nicoli, Francesco; Gallerani, Eleonora; Sforza, Fabio; Finessi, Valentina; Chachage, Mkunde; Geldmacher, Christof; Cafaro, Aurelio; Ensoli, Barbara; Caputo, Antonella; Gavioli, Riccardo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2384282
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