Investigating mechanisms for limited CD8 T-cell expansion in experimental visceral leishmaniasis. (40.5)

• Published in: The Journal of immunology (1950) Vol. 184; no. 1_Supplement; pp. 40 - 40.5
• Main Authors: Bankoti, Rashmi, Stager, Simona
• Format: Journal Article
• Language: English
• Published: 01.04.2010
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.40.5

Abstract Leishmania donovani, a causative agent of visceral leishmaniasis, establishes chronic infections in the spleen in humans and in mice. Thus far, the only cells that are known to be able to reduce the splenic parasite burden following immunotherapy in mice are antigen-specific CD8+ T-cells. Yet, L. donovani appears to be able to evade this defense by limiting the expansion and effector functions of CD8+ T-cell responses. Since a strong clonal expansion of antigen-specific CD8+ T-cells has been shown to be essential for the control of several pathogens, we are particularly interested in dissecting the mechanisms by which L. donovani interferes with the expansion of Leishmania-specific CD8+ T-cells. We first investigated possible inhibitory pathways that may be involved in the suppression of expansion of CD8+ T-cells. Surprisingly, we found that blocking either B7H1 or LAG-3 did not affect the early expansion and functionality of CD8+ T cells. We next evaluated the possible role of IL-10 in limiting the expansion of CD8+ T cells. IL-10R blockade resulted in increased expansion and greater cytotoxic capacity of parasite-specific CD8+ T-cells. However, depletion of Tregs and/or NK cells, which are thought to be the major sources of IL-10 during acute infection, did not improve the magnitude of expansion nor the ability of CD8+ T cells to produce Granzyme B and IFN-γ. Other IL-10 producing cell populations and inhibitory pathways will be discussed.