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

Abstract

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(+)CD45RB(high) 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(+)C45RB(high) 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 CD45RB(high) T cells. Severe colitis could, however, be induced in nude mice by transfer of activated/T(h)1 CD4(+)CD45RB(low) 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.

T cell-induced inflammation of the small and large intestine in immunodeficient mice

“…Lymphocytes were obtained from the spleen, intestine, and colon and analyzed by flow cytometry as previously described (15). Briefly, spleens were removed from WT, RAG KO, and TCR KO mice reconstituted with either CD45RB high T cells, CD45RB low T cells, or PBS and teased into a single cell suspension using the frosted ends of two glass slides in 4% FACS buffer on ice.…”

“…Lamina propria (LP) lymphocytes (LPLs) were prepared by digestion of the finely minced intestinal pieces remaining after IEL isolation with RPMI-1640 -4% FBS solution containing collagenase type VIII (200 U/ml) for 40 min at 250 rpm in a 37°C shaker (15). Lymphocytes were further enriched by centrifugation over a 40% Percoll gradient.…”

The natural compound celastrol inhibits necroptosis and alleviates ulcerative colitis in mice

“…Thin (3.0 μm) paraffin sections were cut continuously to have longitudinal sections of the entire length of the colon tissue on one slide. Slides were stained by H&E and analyzed in a blinded fashion, and scored according to the criteria listed in Table 2 [13][14].…”

T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade

“…Like the IL-10 Ϫ/Ϫ model, the T cell transfer model is responsive to a variety of different immunological and antibiotic treatment protocols. Although the original reports describing this model suggested that the inflammation was confined exclusively to the colon, more recent data demonstrated that the transfer of naive T cells into recombinase activating gene-1-deficient (RAG Ϫ/Ϫ ) mice induces both colitis and small bowel inflammation, making this a model similar to Crohn's disease (12,18). Finally, this model is ideal to study the role that regulatory T cells (Tregs) play in suppressing or limiting the onset and/or perpetuation of intestinal and colonic inflammation.…”