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 CD45RB high 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 CD45RB high -induced transfer colitis effectively, whereas no effect was observed after transfer of nontransduced CD4 + cells. IL-10–GFP CD45RB high 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 CD45RB high -induced transfer colitis. This approach may induce long-term maintenance of mucosal immune homeostasis in Crohn's disease. GASTROENTEROLOGY 2002;123:1865-1876