Selective deficiency of STAT1 in CD4+ T cells enhances susceptibility to Leishmania major infection not by preventing induction of Th1 response, but by impairing CD4+ T cell homing (44.26)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.44-44.26
• Main Authors: Snider, Heidi M, Bhardwaj, Neeti, Barbi, Joseph, Lezama-Davila, Claudio M, Durbin, Joan E, Satoskar, Abhay R
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.44.26

We previously reported that STAT1 signaling is indispensable for host resistance against Leishmania major. In this study, we examined the role of STAT1 in lymphocytes as well as CD4+ versus CD8+ T cells in mediating immunity to L. major by performing adoptive transfers of T cells from WT and STAT1-/- C57BL/6 mice to Rag2-/- C57BL/6 mice. Rag2-/- mice reconstituted with STAT1-/- splenocytes (B cells and T cells) failed to mount an efficient Th1 response following L. major infection, produced more IL-4 and developed large lesions full of parasites. In contrast, Rag2-/- mice reconstituted with WT (STAT1+/+) splenocytes mounted a Th1 response and developed self-resolving lesions. Studies using Rag2-/- recipients that received a combination of purified CD4+ and CD8+ T cells from WT or STAT1-/- mice revealed that STAT1 in CD4+, but not CD8+ T cells was indispensable for immunity against L. major. Further studies using Thy1.1+ congenic recipients receiving WT or STAT1 Thy1.2+ CD4+ cells showed that STAT1 in CD4+ T cells was not required for Th1 differentiation and IFN-γ production during L. major infection, but was critical for migration to regional lymph nodes and the cutaneous site of infection. Together these studies indicate that STAT1 signaling in CD4+ T cells plays a critical role in immunity against L. major by controlling migration of Th1 cells to the site of infection rather than their generation. Research Support: NIH