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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / pathology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology*
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Cell Survival / genetics
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Cell Survival / immunology
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Female
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H-2 Antigens / genetics*
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class II / genetics
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Inflammatory Bowel Diseases / genetics
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Inflammatory Bowel Diseases / immunology
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Inflammatory Bowel Diseases / pathology
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Islets of Langerhans / pathology
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / immunology
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Lymphoproliferative Disorders / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Nuclear Proteins / deficiency
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Nuclear Proteins / genetics
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Trans-Activators / deficiency
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Trans-Activators / genetics
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beta 2-Microglobulin / deficiency
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beta 2-Microglobulin / genetics
Substances
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H-2 Antigens
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H-2Kb protein, mouse
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class II
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MHC class II transactivator protein
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Nuclear Proteins
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Trans-Activators
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beta 2-Microglobulin