Back to Search
Start Over
B7-H1 Blockade Increases Survival of Dysfunctional CD8+ T Cells and Confers Protection against Leishmania donovani Infections.
- Source :
- PLoS Pathogens; May2009, Vol. 5 Issue 5, p1-14, 14p, 7 Graphs
- Publication Year :
- 2009
-
Abstract
- Experimental visceral leishmaniasis (VL) represents an exquisite model to study CD8<superscript>+</superscript> T cell responses in a context of chronic inflammation and antigen persistence, since it is characterized by chronic infection in the spleen and CD8<superscript>+</superscript> T cells are required for the development of protective immunity. However, antigen-specific CD8<superscript>+</superscript> T cell responses in VL have so far not been studied, due to the absence of any defined Leishmania-specific CD8<superscript>+</superscript> T cell epitopes. In this study, transgenic Leishmania donovani parasites expressing ovalbumin were used to characterize the development, function, and fate of Leishmania-specific CD8<superscript>+</superscript> T cell responses. Here we show that L. donovani parasites evade CD8<superscript>+</superscript> T cell responses by limiting their expansion and inducing functional exhaustion and cell death. Dysfunctional CD8<superscript>+</superscript> T cells could be partially rescued by in vivo B7-H1 blockade, which increased CD8<superscript>+</superscript> T cell survival but failed to restore cytokine production. Nevertheless, B7-H1 blockade significantly reduced the splenic parasite burden. These findings could be exploited for the design of new strategies for immunotherapeutic interventions against VL. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 5
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 45437942
- Full Text :
- https://doi.org/10.1371/journal.ppat.1000431