| First Author | Tseveleki V | Year | 2004 |
| Journal | J Immunol | Volume | 173 |
| Issue | 11 | Pages | 6619-26 |
| PubMed ID | 15557152 | Mgi Jnum | J:94365 |
| Mgi Id | MGI:3512647 | Doi | 10.4049/jimmunol.173.11.6619 |
| Citation | Tseveleki V, et al. (2004) Cellular FLIP (long isoform) overexpression in T cells drives Th2 effector responses and promotes immunoregulation in experimental autoimmune encephalomyelitis. J Immunol 173(11):6619-26 |
| abstractText | Cellular FLIP (c-FLIP) is an endogenous inhibitor of death receptor-induced apoptosis through the caspase 8 pathway. It is an NF-kappaB-inducible protein thought to promote the survival of T cells upon activation, and its down-regulation has been implicated in activation-induced cell death. We have generated transgenic mice overexpressing human c-FLIP long form (c-FLIP(L)) specifically in T cells using the CD2 promoter (TgFLIP(L)). TgFLIP(L) mice exhibit increased IgG1 production upon stimulation by a T cell-dependent Ag and a markedly enhanced contact hypersensitivity response to allergen. In addition to showing augmented Th2-type responses, TgFLIP(L) mice are resistant to the development of myelin oligodendrocyte glycoprotein 35-55 peptide-induced experimental autoimmune encephalomyelitis, a Th1-driven autoimmune disease. In vitro analyses revealed that T cells of TgFLIP(L) mice proliferate normally, but produce higher levels of IL-2 and show preferential maturation of Th2 cytokine-producing cells in response to antigenic stimulation. After adoptive transfer, these (Th2) cells protected wild-type recipient mice from experimental autoimmune encephalomyelitis induction. Our results show that the constitutive overexpression of c-FLIP(L) in T cells is sufficient to drive Th2 polarization of effector T cell responses and indicate that it might function as a key regulator of Th cell differentiation. |
