The HIV Tat protein favors the activation of CD8 T cells thus contributing to HIV-related immune dysfunctions
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1
University of Ferrara, Life Sciences and Biotechnology, Italy
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2
University of Padova, Molecular Medicine, Italy
Tat is a regulatory protein produced very early after HIV infection, necessary for viral gene expression, cell-to-cell virus transmission and disease progression. Tat can be released extracellularly and, upon release, enter uninfected T cells displaying several functions, only partially characterized. A large number of studies show an immunomodulatory effect of Tat on CD4 T Lymphocytes and professional APCs, demonstrating how Tat increases their activation and the secretion of pro-inflammatory cytokines and proposing a contribution of Tat to the chronic immune activation described during HIV infection.
CD8 T cells from HIV infected subjects are also characterized by several dysfunctions, including an increased activation. However, whether Tat can modulate also the CD8 T cell response is not clear.
To characterize the role of Tat on CD8 T cell activation, PBLs form healthy donors were stimulated with anti-CD3/CD28 in the presence or absence of Tat protein. Both CD4 and CD8 T cells activated in the presence of Tat showed an enhanced pro-inflammatory cytokine production compared to T cells activated without Tat. Furthermore, memory CD8 T cells from EBV positive donors were stimulated with EBV peptides in the presence or absence of Tat. EBV-specific CTLs generated in the presence of Tat exhibited enhanced effector functions compared to CTLs generated without Tat. The same effect was observed on naïve CD8 T cells primed with CD8 peptide epitopes.
Taken together, these results suggest that the Tat protein of HIV enhances the stimulation of CD8 T cells thus contributing to immune activation during the course of HIV.
Keywords:
HIV-Tat,
CD8 T cells,
Lymphocyte Activation,
HIV Infections,
immune activation,
Memory CD8+ T cells,
CD4 T cells
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Sforza
F,
Nicoli
F,
Finessi
V,
Gallerani
E,
Caputo
A and
Gavioli
R
(2013). The HIV Tat protein favors the activation of CD8 T cells thus contributing to HIV-related immune dysfunctions.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00777
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Received:
17 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Fabio Sforza, University of Ferrara, Life Sciences and Biotechnology, Ferrara, 44121, Italy, sfrfba@unife.it