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.