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Nicoli, Francesco; Gallerani, Eleonora; Sforza, Fabio; Finessi, Valentina; Chachage, Mkunde; Geldmacher, Christof; Cafaro, Aurelio; Ensoli, Barbara; Caputo, Antonella; Gavioli, Riccardo (2018): The HIV-1 Tat protein affects human CD4(+) T-cell programing and activation, and favors the differentiation of naive CD4(+) T cells. In: Aids, Vol. 32, No. 5: pp. 575-581
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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 naive 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 naive 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, IFN and TNF in CD4(+) T cells, as well as the upregulation of T-bet and Eomes expression. Naive 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 naive CD4(+) T cells.