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AIDS. 2018 Mar 13;32(5):575-581. doi: 10.1097/QAD.0000000000001734.

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

Author information

1
Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara.
2
Department of Molecular Medicine, University of Padova, Padova, Italy.
3
Department of Immunology, NIMR Mbeya Medical Research Centre, Mbeya, Tanzania.
4
Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU).
5
German Center for Infection Research (DZIF), Partner Site Munich, Munich, Germany.
6
National AIDS Center, Istituto Superiore di Sanità, Rome, Italy.

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.

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