Article: article from journal or magazin.
MHC-II-independent CD4+ T cells induce colitis in immunodeficient RAG-/- hosts.
Journal of Immunology
CD4(+) alpha beta T cells from either normal C57BL/6 (B6) or MHC-II-deficient (A alpha(-/-) or A beta(-/-)) B6 donor mice engrafted into congenic immunodeficient RAG1(-/-) B6 hosts induced an aggressive inflammatory bowel disease (IBD). Furthermore, CD4(+) T cells from CD1d(-/-) knockout (KO) B6 donor mice but not those from MHC-I(-/-) (homozygous transgenic mice deficient for beta(2)-microglobulin) KO B6 mice induced a colitis in RAG(-/-) hosts. Abundant numbers of in vivo activated (CD69(high)CD44(high)CD28(high)) NK1(+) and NK1(-) CD4(+) T cells were isolated from the inflamed colonic lamina propria (cLP) of transplanted mice with IBD that produced large amounts of TNF-alpha and IFN-gamma but low amounts of IL-4 and IL-10. IBD-associated cLP Th1 CD4(+) T cell populations were polyclonal and MHC-II-restricted when derived from normal B6 donor mice, but oligoclonal and apparently MHC-I-restricted when derived from MHC-II-deficient (A alpha(-/-) or A beta(-/-)) B6 donor mice. cLP CD4(+) T cell populations from homozygous transgenic mice deficient for beta(2)-microglobulin KO B6 donor mice engrafted into RAG(-/-) hosts were Th2 and MHC-II restricted. These data indicate that MHC-II-dependent as well as MHC-II-independent CD4(+) T cells can induce a severe and lethal IBD in congenic, immunodeficient hosts, but that the former need the latter to express its IBD-inducing potential.
Adoptive Transfer, Animals, Antigens, CD1/genetics, Antigens, CD1d, CD4-Positive T-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/metabolism, Cell Membrane/immunology, Cell Membrane/metabolism, Colitis/genetics, Colitis/immunology, Cytokines/biosynthesis, Dose-Response Relationship, Immunologic, Histocompatibility Antigens Class I/genetics, Histocompatibility Antigens Class II/genetics, Histocompatibility Antigens Class II/physiology, Homeodomain Proteins/genetics, Immunologic Deficiency Syndromes/genetics, Immunologic Deficiency Syndromes/immunology, Immunophenotyping, Inflammatory Bowel Diseases/genetics, Inflammatory Bowel Diseases/immunology, Injections, Intraperitoneal, Intestinal Mucosa/immunology, Intestinal Mucosa/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, Antigen, T-Cell, alpha-beta/administration &, dosage, Spleen/cytology, Spleen/immunology, Th1 Cells/immunology, Th1 Cells/metabolism, beta 2-Microglobulin/deficiency, beta 2-Microglobulin/genetics
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