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International Immunology, Vol. 16, No. 1, pp. 77-89, January 2004
© 2004 Japanese Society for Immunology

FEATURED ARTICLE OF THE MONTH

Regulation of chronic colitis in athymic nu/nu (nude) mice

F. Stephen Laroux1, Hillary H. Norris2, Jeff Houghton1, Kevin P. Pavlick1, Sulaiman Bharwani3, Dana M. Merrill4, John Fuseler4, Robert Chervenak2 and Matthew B. Grisham1

Departments of 1 Molecular and Cellular Physiology, 2 Microbiology and Immunology, 3 Pediatrics and 4 Medicine, Louisiana State University Health Sciences Center, Shreveport, 1501 Kings Highway, LA 71130, USA

Correspondence to: M. B. Grisham; E-mail: mgrish{at}lsuhsc.edu
Transmitting editor: C. Terhorst

The objective of this study was to assess the roles of NK cells, B cells and/or intraepithelial lymphocytes (IEL) in suppressing the development of colitis in nude mice reconstituted with CD4+CD45RBhigh T cells. BALB/c nude mice were lethally irradiated and reconstituted with bone marrow from different immunodeficient mice to generate athymic chimeras devoid of one or more lymphocyte populations. Transfer of CD4+C45RBhigh T cells into chimeric recipients devoid of B cells, T cells and IEL produced severe colitis within 6–8 weeks, whereas transfer of these same T cells into B cell- and T cell-deficient or T cell-deficient chimeras produced little to no gut inflammation. In addition, we found that nude mice depleted of NK cells or RAG-1–/– mice reconstituted with IEL failed to develop colitis following transfer of CD45RBhigh T cells. Severe colitis could, however, be induced in nude mice by transfer of activated/Th1 CD4+CD45RBlow T cells. Taken together, our data suggest that IEL, but not B cells or NK cells, play an important role in suppressing the development of chronic colitis in this model. In addition, our data demonstrate that suppression of disease may be due to polarization of naive CD4+ cells toward a non-pathogenic and/or regulatory phenotype.

Keywords: B cell, Crohn’s disease, inflammatory bowel disease, intraepithelial lymphocyte, NK cell, T cell


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