Cellular FLIP long isoform transgenic mice overcome inherent Th2-biased immune responses to efficiently resolve Leishmania major infection.

Abstract

c-FLIP(L) expression in T cells is required for mounting effective T cell responses and can also be critical for effector T cell differentiation, as has recently been shown by a number of in vivo studies in conditional knockout and transgenic mouse systems. Available data supports therefore a novel immunomodulatory role of this anti-apoptotic protein besides its traditionally proposed function in homeostatic maintenance of T cell populations. In this study, the responses to infection with Leishmania major of mice over-expressing FLIP(L) specifically in the T cell compartment (TgFLIP(L)) are assessed. Although previous studies have shown that FLIP(L) drives T cells towards a T(h)2 differentiation programme in various autoimmune and allergic paradigms, in this study, we show that TgFLIP(L) are able to overcome this T(h)2 bias in a dermal L. major infection model to mount a robust T(h)1 response to pathogen and effectively clear infection. Our results suggest that vaccination protocols designed to enhance FLIP(L) expression in T cells may be useful for the treatment of autoimmune diseases like multiple sclerosis, without necessarily compromising immune responses towards infectious agents.

• Authors: Vivian Tseveleki, Panagiotis Tsagozis, Olga Koutsoni, Eleni Dotsika, Lesley Probert
• Journal: International immunology (Int Immunol) Vol. 19 Issue 10 Pg. 1183-9 (Oct 2007) ISSN: 0953-8178 [Print] England
• PMID: 17878261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• CASP8 and FADD-Like Apoptosis Regulating Protein
• Cflar protein, mouse
• Cytokines
• Protein Isoforms

Topics

• Animals
• Antigens, Protozoan (immunology)
• CASP8 and FADD-Like Apoptosis Regulating Protein (genetics, metabolism)
• Cytokines (metabolism)
• Immunologic Memory
• Leishmania major
• Leishmaniasis, Cutaneous (immunology)
• Mice
• Mice, Transgenic
• Protein Isoforms (genetics, metabolism)
• Th2 Cells (immunology)
• Up-Regulation