Prevention of colitis by interleukin 10–transduced T lymphocytes in the SCID mice transfer model

Abstract

Background & Aims: Regulatory CD4+ cells secreting the anti-inflammatory cytokine interleukin (IL)-10 play a key role in maintaining the immune balance in the intestinal mucosa. In this study we engineered primary CD4+ cells to express IL-10 and investigated the efficacy of this approach in offering protection against experimental colitis. Methods: Spleen-derived CD4+ cells were transduced by using a retroviral vector to simultaneously express IL-10 and green fluorescent protein (GFP). The therapeutic benefit of CD4+ cells transduced with IL-10 GFP was studied in experimental colitis, induced by transfer of CD45RBhigh CD4+ cells to severe combined immunodeficient mice, and in acute trinitrobenzene sulfonic acid (TNBS)–induced colitis. Results: Transferred engineered GFP fluorescent cells were detected for at least 15 weeks in peripheral blood, spleens, colon, and lymph nodes draining the intestine of recipient SCID mice. IL-10–GFP CD4+ cells prevented CD45RBhigh-induced transfer colitis effectively, whereas no effect was observed after transfer of nontransduced CD4+ cells. IL-10–GFP CD45RBhigh CD4+ cells lost the capacity to induce colitis. By contrast, no therapeutic benefit was observed in TNBS-induced colitis. Conclusions: Primary murine CD4+ cells that were engineered to express IL-10 by retroviral transduction act as regulatory cells in CD45RBhigh-induced transfer colitis. This approach may induce long-term maintenance of mucosal immune homeostasis in Crohn's disease.GASTROENTEROLOGY 2002;123:1865-1876