Title: Self-antigen recognition by TGF beta1-deficient T cells causes their activation and systemic inflammation.

Authors: Bommireddy, Ramireddy; Pathak, Leena J; Martin, Jennifer; Ormsby, Ilona; Engle, Sandra J; Boivin, Gregory P; Babcock, George F; Eriksson, Anna U; Singh, Ram R; Doetschman, Thomas

Published In Lab Invest, (2006 Oct)

Abstract: To investigate whether the multifocal inflammatory disease in TGFbeta1-deficient mice is caused by self-antigen (self-Ag)-specific autoreactive T cells, or whether it is caused by antigen independent, spontaneous hyperactivation of T cells, we have generated Tgfb1(-/-) and Tgfb1(-/-) Rag1(-/-) mice expressing the chicken OVA-specific TCR transgene (DO11.10). On a Rag1-sufficient background, Tgfb1(-/-) DO11.10 mice develop a milder inflammation than do Tgfb1(-/-) mice, and their T cells display a less activated phenotype. The lower level of activation correlates with the expression of hybrid TCR (transgenic TCRbeta and endogenous TCRalpha), which could recognize self-Ag and undergo activation. In the complete absence of self-Ag recognition (Tgfb1(-/-) DO11.10 Rag1(-/-) mice) inflammation and T-cell activation are eliminated, demonstrating that self-Ag recognition is required for the hyper-responsiveness of TGFbeta1-deficient T cells. Thus, TGFbeta1 is required for the prevention of autoimmune disease through its ability to control the activation of autoreactive T cells to self-Ag.

PubMed ID: 16865088

MeSH Terms: Animals; Autoantigens/immunology; Autoimmunity/immunology*; Inflammation/immunology; Inflammation/pathology; Mice; Mice, Knockout; Mice, Transgenic; T-Lymphocytes/immunology*; Transforming Growth Factor beta1/immunology*