title: Self-antigen recognition by TGF beta1-deficient T cells causes their activation and systemic inflammation.
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.
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Ramireddy
authors.initials: R
authors.lastname: Bommireddy
authors.forename: Leena J
authors.initials: LJ
authors.lastname: Pathak
authors.forename: Jennifer
authors.initials: J
authors.lastname: Martin
authors.forename: Ilona
authors.initials: I
authors.lastname: Ormsby
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Engle
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Boivin
authors.forename: George F
authors.initials: GF
authors.lastname: Babcock
authors.forename: Anna U
authors.initials: AU
authors.lastname: Eriksson
authors.forename: Ram R
authors.initials: RR
authors.lastname: Singh
authors.forename: Thomas
authors.initials: T
authors.lastname: Doetschman
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000276:immunology*
chemical_list: D001324:Autoantigens; D053773:Transforming Growth Factor beta1