Prevention of colitis by interleukin 10-transduced T lymphocytes in the SCID mice transfer model.
OBJECTIVE
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.
Van Montfrans
Catherine
C
Department of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Rodriguez Pena
Maria Sol
MS
Pronk
Inge
I
Ten Kate
Fiebo J W
FJ
Te Velde
Anje A
AA
Van Deventer
Sander J H
SJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D002470:Cell Survival; D003092:Colitis / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007202:Indicators and Reagents; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008164:Luminescent Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D014161:Transduction, Genetic; D014302:Trinitrobenzenesulfonic Acid
D016207:Cytokines; D007202:Indicators and Reagents; D018836:Inflammation Mediators; D008164:Luminescent Proteins; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D014302:Trinitrobenzenesulfonic Acid; D017493:Leukocyte Common Antigens