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International Immunology Advance Access originally published online on September 18, 2007
International Immunology 2007 19(10):1183-1189; doi:10.1093/intimm/dxm089
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© The Author 2007. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press and The Japanese Society for Immunology are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oupjournals.org

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

Vivian Tseveleki1, Panagiotis Tsagozis2, Olga Koutsoni2, Eleni Dotsika2 and Lesley Probert1

1 Laboratory of Molecular Genetics
2 Laboratory of Cellular Immunology, Hellenic Pasteur Institute, 127 Vasilissis Sophias Avenue, 115 21 Athens, Greece

Correspondence to: L. Probert; Email: lesley{at}pasteur.gr

c-FLIPL 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 FLIPL specifically in the T cell compartment (TgFLIPL) are assessed. Although previous studies have shown that FLIPL drives T cells towards a Th2 differentiation programme in various autoimmune and allergic paradigms, in this study, we show that TgFLIPL are able to overcome this Th2 bias in a dermal L. major infection model to mount a robust Th1 response to pathogen and effectively clear infection. Our results suggest that vaccination protocols designed to enhance FLIPL expression in T cells may be useful for the treatment of autoimmune diseases like multiple sclerosis, without necessarily compromising immune responses towards infectious agents.

Keywords: apoptosis, parasite infection, Th cell differentiation, vaccines

Transmitting editor: D. Wallach

Received 7 December 2006, accepted 9 July 2007.


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[Abstract] [Full Text] [PDF]


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