Journal Article

CD4 T cells monospecific to ovalbumin produced by <i>Escherichia coli</i> can induce colitis upon transfer to BALB/c and SCID mice

Masaru Yoshida, Tomohiro Watanabe, Takashi Usui, Yoichi Matsunaga, Yasuhiko Shirai, Masashi Yamori, Toshiyuki Itoh, Sonoko Habu, Tsutomu Chiba, Toru Kita and Yoshio Wakatsuki

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 13, issue 12, pages 1561-1570
Published in print December 2001 | ISSN: 0953-8178
Published online December 2001 | e-ISSN: 1460-2377 | DOI:
CD4 T cells monospecific to ovalbumin produced by Escherichia coli can induce colitis upon transfer to BALB/c and SCID mice

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Although some animal models suggest an involvement of CD4 T cells reactive to luminal microrbial 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-γ 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.

Keywords: animal model; bacterial flora; Crohn's disease; cytokines; inflammatory bowel disease; mucosa; transgenic mice; ulcerative colitis; APC antigen-presenting cell; ECLacZ Escherichia coli expressing LacZ; ECOVA Escherichia coli expressing ovalbumin; HSA human serum antigen; IBD inflammatory bowel disease; LacZ β-galactosidase; LP lamina propria; OVA ovalbumin

Journal Article.  6830 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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