Virus-Induced Activation of Self-Specific TCRαβ CD8αα Intraepithelial Lymphocytes Does Not Abolish Their Self-Tolerance in the Intestine

作者: Leslie Saurer , Inge Seibold , Silvia Rihs , Claudio Vallan , Tilman Dumrese

DOI: 10.4049/JIMMUNOL.172.7.4176

关键词: Intestinal mucosaAutoimmunityLymphocytic choriomeningitisBiologyCytotoxic T cellIntraepithelial lymphocyteT-cell receptorMolecular mimicryProinflammatory cytokineImmunology

摘要: TCRαβ CD8αα intestinal intraepithelial lymphocytes (IEL) represent an enigmatic subset of T cells, particularly, in regard to their potential functions and the apparent persistence cells expressing self-specific TCR. We have used mice that are transgenic for specific lymphocytic choriomeningitis virus (LCMV)-derived peptide gp33, TCRαβ-transgenic coexpress gp33 Ag ubiquitously, analyze functional properties IEL presence, or absence, MHC-restricted Ag, assess impact molecular mimicry during a potent LCMV infection on potentially self-reactive IEL. In this study, we show presence self-Ag results reduced expression IL-2, IFN-γ, IL-10 by resident while mRNA TGFβ is not affected. further demonstrate despite secluded location epithelium, activated after mucosa with LCMV. Importantly, LCMV-induced activation does reverse tolerance as no cytotoxic activity up-regulated proinflammatory cytokines detected overt signs autoimmunity seen. Taken together, these support immunoregulatory role clearly speak against involvement cell inflammatory reactions tissue destruction.

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