Abstract:
:Experimental visceral leishmaniasis (VL) represents an exquisite model to study CD8(+) T cell responses in a context of chronic inflammation and antigen persistence, since it is characterized by chronic infection in the spleen and CD8(+) T cells are required for the development of protective immunity. However, antigen-specific CD8(+) T cell responses in VL have so far not been studied, due to the absence of any defined Leishmania-specific CD8(+) 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(+) T cell responses. Here we show that L. donovani parasites evade CD8(+) T cell responses by limiting their expansion and inducing functional exhaustion and cell death. Dysfunctional CD8(+) T cells could be partially rescued by in vivo B7-H1 blockade, which increased CD8(+) 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.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Joshi T,Rodriguez S,Perovic V,Cockburn IA,Stäger Sdoi
10.1371/journal.ppat.1000431subject
Has Abstractpub_date
2009-05-01 00:00:00pages
e1000431issue
5eissn
1553-7366issn
1553-7374journal_volume
5pub_type
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