Tseveleki Vivian, Tsagozis Panagiotis, Koutsoni Olga, Dotsika Eleni, Probert Lesley
Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 127 Vasilissis Sophias Avenue, 115 21 Athens, Greece.
Int Immunol. 2007 Oct;19(10):1183-9. doi: 10.1093/intimm/dxm089. Epub 2007 Sep 18.
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.
T细胞中c-FLIP(L)的表达对于产生有效的T细胞反应是必需的，并且对于效应T细胞的分化也可能至关重要，最近在条件性敲除和转基因小鼠系统中的多项体内研究表明了这一点。因此，现有数据支持这种抗凋亡蛋白除了在T细胞群体的稳态维持中传统上所提出的功能外，还具有一种新的免疫调节作用。在本研究中，评估了在T细胞区室中特异性过表达FLIP(L)的小鼠（TgFLIP(L)）对硕大利什曼原虫感染的反应。尽管先前的研究表明，在各种自身免疫和过敏模型中，FLIP(L)会驱动T细胞向Th2分化程序发展，但在本研究中，我们表明TgFLIP(L)能够在皮肤硕大利什曼原虫感染模型中克服这种Th2偏向，以对病原体产生强大的Th1反应并有效清除感染。我们的结果表明，旨在增强T细胞中FLIP(L)表达的疫苗接种方案可能对治疗自身免疫性疾病如多发性硬化症有用，而不一定会损害对感染因子的免疫反应。
