MHC-II-Independent CD4(+) T cells induce colitis in immunodeficient RAG(-/-) hosts

CD4(+) alpha betaT cells from either normal C57BL/6 (B6) or MHC-II-deficien t (A alpha (-/-) or A beta (-/-)) B6 donor mice engrafted into congenic imm unodeficient RAG1(-/-) B6 hosts induced an aggressive inflammatory bowel di sease (IBD), Furthermore, CD4+ T cells from CDld(-/-) knockout (KO) B6 dono r mice but not those from MHC-I-/- (homozygous transgenic mice deficient fo r beta (2)-micro-globulin) 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 LED 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 whe n derived from normal B6 donor mice, but oligoclonal and apparently MHC-I-r estricted when derived from MHC-LI-deficient (A alpha (-/-) or A beta (-/-) ) B6 donor mice. cLP CD4(+) T cell populations from homozygous transgenic m ice deficient for beta (2)-microglobulin KO B6 donor mice engrafted into RA G(-/-) hosts were Th2 and MHC-II restricted, These data indicate that MHC-I I-dependent as well as MHC-II-independent CD4(+) T cells can induce a sever e and lethal PBD in congenic, immunodeficient hosts, but that the former ne ed the latter to express its IBD-inducing potential.