Self-antigen recognition by TGFβ1-deficient T cells causes their activation and systemic inflammation

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

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

To investigate whether the multifocal inflammatory disease in TGFβ1-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 TCRβ and endogenous TCRα), 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 TGFβ1-deficient T cells. Thus, TGFβ1 is required for the prevention of autoimmune disease through its ability to control the activation of autoreactive T cells to self-Ag.

Original languageEnglish (US)
Pages (from-to)1008-1019
Number of pages12
JournalLaboratory Investigation
Volume86
Issue number10
DOIs
StatePublished - Oct 7 2006

Keywords

  • Autoimmunity
  • Inflammation
  • Knockout
  • Self-antigen
  • T cells
  • TGFβ1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Bommireddy, R., Pathak, L. J., Martin, J., Ormsby, I., Engle, S. J., Boivin, G. P., Babcock, G. F., Eriksson, A. U., Singh, R. R., & Doetschman, T. (2006). Self-antigen recognition by TGFβ1-deficient T cells causes their activation and systemic inflammation. Laboratory Investigation, 86(10), 1008-1019. https://doi.org/10.1038/labinvest.3700460