MHC-II-independent CD4+ T cells induce colitis in immunodeficient RAG-/- hosts.
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.
Department of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany.
Z
Z
Trobonjaca
F
F
Leithäuser
P
P
Möller
H
H
Bluethmann
Y
Y
Koezuka
H R
HR
MacDonald
J
J
Reimann
D019264:Adoptive Transfer; D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003092:Colitis / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D018949:Antigens, CD1; D055610:Antigens, CD1d; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; C064658:RAG-1 protein