The HIV-1 Tat protein affects human CD4(+) T-cell programing and activation, and favors the differentiation of naive CD4(+) T cells

Nicoli, Francesco; Gallerani, Eleonora; Sforza, Fabio; Finessi, Valentina; Chachage, Mkunde; Geldmacher, Christof; Cafaro, Aurelio; Ensoli, Barbara; Caputo, Antonella and 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

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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0269-9370
• Alliance/National Licence: This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
• Language: English