Pivotal roles of CD8+ T cells restricted by MHC class I-like molecules in autoimmune diseases

Gobardhan Das, Jyoti Das, Paul Eynott, Yingyu Zhang, Alfred L.M. Bothwell, Luc Van Kaer, Yufang Shi

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Unlike T cells restricted by major histocompatibility complex (MHC) class Ia or class II molecules, T cells restricted by MHC class I-like molecules demonstrate properties of both innate and adaptive immunity and are therefore considered innate-like lymphocytes (ILLs). ILLs are believed to have immunoregulatory functions, but their roles in autoimmunity and defense against infections remain elusive. To study the properties of ILLs, we generated mice expressing only MHC class I-like molecules by crossing CIITA-/- with Kb-/-Db-/- mice. Surprisingly, these mice developed a lymphoproliferative syndrome and autoimmunity, most notably inflammatory bowel disease (IBD) and insulitis. The CD8+ ILLs in these mice exhibit a constitutively activated phenotype, and depletion of these cells abolished the autoimmune disorders. In addition, adoptive transfer of CD8+ ILLs from Kb-/-Db-/-CIITA-/- mice to Rag-1 -/-pfn-/- mice also resulted in IBD and insulitis. These findings provide direct evidence that CD8+ ILLs are sufficient to initiate and mediate autoimmune diseases. JEM

Original languageEnglish (US)
Pages (from-to)2603-2611
Number of pages9
JournalJournal of Experimental Medicine
Volume203
Issue number12
DOIs
StatePublished - Nov 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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