HIV-1 impairs in vitro priming of naïve T cells and gives rise to contact-dependent suppressor T cells
Open Access
- 10 May 2010
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 40 (8), 2248-2258
- https://doi.org/10.1002/eji.201040377
Abstract
Priming of T cells in lymphoid tissues of HIV-infected individuals occurs in the presence of HIV-1. DC in this milieu activate T cells and disseminate HIV-1 to newly activated T cells, the outcome of which may have serious implications in the development of optimal antiviral responses. We investigated the effects of HIV-1 on DC–naïve T-cell interactions using an allogeneic in vitro system. Our data demonstrate a dramatic decrease in the primary expansion of naïve T cells when cultured with HIV-1-exposed DC. CD4+ and CD8+ T cells showed enhanced expression of PD-1 and TRAIL, whereas CTLA-4 expression was observed on CD4+ T cells. It is worth noting that T cells primed in the presence of HIV-1 suppressed priming of other naïve T cells in a contact-dependent manner. We identified PD-1, CTLA-4, and TRAIL pathways as responsible for this suppresion, as blocking these negative molecules restored T-cell proliferation to a higher degree. In conclusion, the presence of HIV-1 during DC priming produced cells with inhibitory effects on T-cell activation and proliferation, i.e. suppressor T cells, a mechanism that could contribute to the enhancement of HIV-1 pathogenesis.Keywords
This publication has 48 references indexed in Scilit:
- In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses, Revealing Rapid Loss of Virus Reactive CD4+ T Cells in Acute HIV-1 InfectionPLOS ONE, 2009
- Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Inhibits Experimental Autoimmune Thyroiditis by the Expansion of CD4+CD25+ Regulatory T CellsEndocrinology, 2008
- How regulatory T cells workNature Reviews Immunology, 2008
- Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaquesProceedings of the National Academy of Sciences of the United States of America, 2007
- Upregulation of PD-1 Expression on Circulating and Intrahepatic Hepatitis C Virus-Specific CD8+T Cells Associated with Reversible Immune DysfunctionJournal of Virology, 2007
- Suppression of HIV-specific T cell activity by lymph node CD25+regulatory T cells from HIV-infected individualsProceedings of the National Academy of Sciences of the United States of America, 2007
- THE B7 FAMILY REVISITEDAnnual Review of Immunology, 2005
- Human Immunodeficiency Virus Type 1 Activates Plasmacytoid Dendritic Cells and Concomitantly Induces the Bystander Maturation of Myeloid Dendritic CellsJournal of Virology, 2004
- Natural versus adaptive regulatory T cellsNature Reviews Immunology, 2003
- PD-1:PD-L inhibitory pathway affects both CD4+ and CD8+ T cells and is overcome by IL-2European Journal of Immunology, 2002