Cutting edge: Inflammatory signals drive organ-specific autoimmunity to normally cross-tolerizing endogenous antigen

Vaiva Vezys, Leo Lefrançois

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Links have been observed between infections and the development of autoimmunity. Proposed explanations include activation of self-Ag-bearing APC. Using a model system in which transgenic OVA is expressed in enterocytes, we showed that CD8 T cell recognition of cross-presented Ag in gut-associated lymph nodes was tolerogenic. However, concomitant infection with vesicular stomatitis virus encoding OVA abrogated tolerance and induced disease. We now show that following transfer of naive OT-I T cells, the addition of wild-type vesicular stomatitis virus, oral cholera toxin, or CD40 triggering can induce intestinal disease in transgenic mice. Tissue damage accompanied dramatic increases in cytokine release by activated OT-I cells in the intestine. The data indicated that products of antigenically unrelated infections can combine with cross-presented self-Ags on APC to prime autoaggressiveness, independent of additional Ag release. These results help explain how diverse pathogens, lacking any homology to self-proteins, could be causative agents in induction of organ-specific autoimmunity.

Original languageEnglish (US)
Pages (from-to)6677-6680
Number of pages4
JournalJournal of Immunology
Volume169
Issue number12
DOIs
StatePublished - Dec 15 2002

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