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

Gastroenterology. 2002 Dec;123(6):1865-76. doi: 10.1053/gast.2002.37067.

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.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / transplantation*
  • Cell Survival
  • Colitis / chemically induced
  • Colitis / etiology
  • Colitis / prevention & control*
  • Cytokines / metabolism
  • Green Fluorescent Proteins
  • Indicators and Reagents
  • Inflammation Mediators / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / therapeutic use*
  • Leukocyte Common Antigens / analysis
  • Luminescent Proteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID / physiology*
  • Spleen / cytology
  • Transduction, Genetic*
  • Trinitrobenzenesulfonic Acid

Substances

  • Cytokines
  • Indicators and Reagents
  • Inflammation Mediators
  • Luminescent Proteins
  • Interleukin-10
  • Green Fluorescent Proteins
  • Trinitrobenzenesulfonic Acid
  • Leukocyte Common Antigens