CD4 T cells monospecific to ovalbumin produced by Escherichia coli can induce colitis upon transfer to BALB/c and SCID mice.
Although some animal models suggest an involvement of CD4 T cells reactive to luminal microbial antigen(s) for the pathogenesis of inflammatory bowel diseases (IBD), direct linkage between microflora-driven clonal expansion of CD4 T cells and the development of colitis has not been well studied. Here, BALB/c and SCID mice were given CD4 T cells purified from Rag-2(-/-) mice crossed to transgenic mice expressing TCR specific to ovalbumin (OVA) then administered with antibiotic-resistant Escherichia coli producing OVA (ECOVA) or LacZ (ECLacZ) via the rectum. The ECOVA-inoculated BALB/c and SCID mice developed a subacute colitis with microscopic features of distortion of crypt architecture, loss of goblet cells, and focal infiltration by mononuclear cells in the lamina propria (LP) and submucosa. Expanding OVA-specific CD4 T cells were detected in colonic follicles of mice with ECOVA. Early in colitis, OVA-specific CD4 T cells producing IFN-gamma predominate in the LP of the colon, which was followed by an emergence of OVA-specific CD4 T cells producing IL-4 and IL-10 at a later time point. Co-transfer of an IL-10-secreting OVA-specific CD4 T cell line prevented colitis. Thus, an expansion of CD4 T cells monospecific to OVA, an antigen non-cross-reactive to colonic tissue, can mediate both induction and inhibition of the colitis which was associated with hyperplasia of lymph follicles.
Yoshida
M
M
Divisions of Clinical Bio-regulatory Science, and Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogo-in, Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Watanabe
T
T
Usui
T
T
Matsunaga
Y
Y
Shirai
Y
Y
Yamori
M
M
Itoh
T
T
Habu
S
S
Chiba
T
T
Kita
T
T
Wakatsuki
Y
Y
D000285:Administration, Rectal; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D002460:Cell Line; D003092:Colitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology*; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007763:Lac Operon / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D019282:Wasting Syndrome / Q000276:immunology
D000942:Antigens, Bacterial; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D016753:Interleukin-10; D010047:Ovalbumin