| Abstrakt: |
Our studies have elucidated, in part, the mechanism whereby persistent stimulation by normal enteric antigens leads to the development of chronic enterocolitis in interleukin 10‐deficient (IL‐10‐/‐) mice. This disease is mediated by IL‐10‐/‐CD4+T cells as evidenced by their ability to transfer colitis to immunodeficient RAG‐2‐/‐mice. Furthermore, the CD4+T cells recovered from the affected colons of IL‐10‐/‐mice consisted of a highly polarized Th1‐like population because they produced interferon‐γ (IFN‐γ) but not IL‐4. We found that enterocolitis could be prevented if 3‐week‐old mutants were treated for 6–8 weeks with either anti‐IL‐12 or anti‐IFN‐γ monoclonal antibodies (mAb). These results were consistent with the findings of in vitro studies suggesting that IFN‐γ and, in particular, IL‐12 direct the differentiation of naive T cells toward a Th1 phenotype. Apparently, the uncontrolled production of IL‐12 and IFN‐γ by accessory cells and T cells, respectively, in IL‐10‐/‐mice ultimately resulted in the excessive generation and activation of Th1 cells, hence, immunopathology. IL‐10‐/‐mice have also been used to evaluate the importance of IL‐10 in regulating immune responses outside of the gastrointestinal (GI) tract. In these studies, IL‐10‐/‐mice were challenged with a variety of foreign antigens using different routes of administration. In general, the results repeatedly demonstrated that a major function of IL‐10 is to protect the host from the harmful side effects of an overly zealous immuneinflammatory response. However, other studies have confirmed speculations that the potent immunosuppressive activities of IL‐10 may, under certain circumstances, increase the host's susceptibility to infection with certain types of pathogenic organisms. J. Leukoc. Biol. 61: 389–396; 1997. |
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