Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: Effects in CD4+-cell depleted, athymic and NK-cell depleted SCID mice

Abstract

Administration of dextran sulfate to mice, given in the drinking water results in acute or subacute colonic inflammation, depending on the administration protocol. This colonic inflammation exhibits ulceration, healing and repair, and a therapeutic response that makes it valuable for the study of mechanisms that could act in the pathogenesis of human ulcerative colitis, a disease thought to have an immunologically dependent pathogenesis. To investigate if immunological mechanisms were involved in the induction of colonic inflammation in this model, mice with different degrees of immunodeficiency were used. It was shown that dextran sulfate induced colitis could be induced in Balb/c mice depleted of CD4(+) helper T cells by treatment with monoclonal antibodies preceded by adult thymectomy. The depletion of CD4(+) was verified by flow cytometric analysis. Furthermore, the colonic inflammation could equally be induced in athymic CD-1 nu/nu mice lacking thymus-derived T cells, in T and B-cell deficient SCID mice, and also in SCID mice depleted of NK cells by treatment with anti-asialo GM1 antibodies. The NK-cell depletion was verified by measuring spleen NK-cell activity. The resulting colonic inflammation in all these types of deficient mice was qualitatively comparable, as shown by clinical and histological appearance. These results indicate that the presence of functional T, B and NK cells is not crucial for the induction of dextran sulfate colitis in mice.

Protection of the intestinal mucosa by intraepithelial γδ T cells

“…Inflammation was also clearly evident by day 5 of DSS treatment. This finding is in agreement with previous observations that inflammation in the DSSinduced colitis model systems is a rather late event that follows histological evidence of tissue damage (24,25).…”

Activation of epithelial CD98 glycoprotein perpetuates colonic inflammation

“…25 Many of the previous CD98 functional studies have used anti-CD98 antibodies as agonists, an approach that has proven useful for the study of signaling in a great many. 26 Indeed, our group has shown that CD98 is involved in signal recognition and transduction in Caco2-BBE cells, 9,12 these signaling events may be mediated through b1 integrins/Ca 2 þ , as CD98 is known to interact with integrins such as b1 integrins and ICAM-1. 12 In the present study, we demonstrate that the CD98 glycoprotein is expressed in Caco2-BBE monolayers, in the human intestine, and in the mouse small and large intestinal mucosa, and sought to better define the function of CD98 in these tissues.…”

Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets

“…The first cells to infiltrate the mucosa and submucosa after DSS challenge are large numbers of neutrophils and macrophages, followed by T and B lymphocytes [19]. The exact role of T and B cells in the DSS colitis model is still not known as various lymphocyte-deficient animals, such as CD4-depleted mice, nude mice and SCID mice, develop similar or aggravated colitis compared with wildtype mice [20,21] manifested as a higher mortality rate after prolonged exposure to DSS. Our data indicate that T cells are affected early in DSS-induced colitis, i.e.…”