MHC-II-Independent CD4+ T Cells Induce Colitis in Immunodeficient RAG-/- Hosts

• Published in: The Journal of immunology (1950) 2001-03, Vol.166 (6), p.3804-3812
• Main Authors: Trobonjaca, Zlatko, Leithauser, Frank, Moller, Peter, Bluethmann, Horst, Koezuka, Yasuhiko, MacDonald, H. Robson, Reimann, Jorg
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antigens, CD1 - genetics; Antigens, CD1d; beta 2-Microglobulin - deficiency; beta 2-Microglobulin - genetics; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - transplantation; 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; Intestinal Mucosa - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, T-Cell, alpha-beta - administration & dosage; Spleen - cytology; Spleen - immunology; Spleen - transplantation; Th1 Cells - immunology; Th1 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.6.3804

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.