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

Das G, Das J, Eynott P, Zhang Y, Bothwell AL, Van Kaer L, Shi Y
J Exp Med. 2006 203 (12): 2603-11

PMID: 17088432 · PMCID: PMC2118151 · DOI:10.1084/jem.20060936

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.

MeSH Terms (19)

Animals Autoimmune Diseases beta 2-Microglobulin CD8-Positive T-Lymphocytes Cell Survival Female H-2 Antigens Histocompatibility Antigen H-2D Histocompatibility Antigens Class II Inflammatory Bowel Diseases Islets of Langerhans Lymphoproliferative Disorders Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Nuclear Proteins Trans-Activators

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