Studies with IL-10-/- mice: an overview.
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-gamma (IFN-gamma) 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-gamma monoclonal antibodies (mAb). These results were consistent with the findings of in vitro studies suggesting that IFN-gamma 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-gamma 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 immune-inflammatory 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.
Rennick
D M
DM
DNAX Research Institute of Molecular and Cellular Biology Inc., Palo Alto, California 94304-1104, USA.
Fort
M M
MM
Davidson
N J
NJ
D000818:Animals; D000917:Antibody Formation; D004760:Enterocolitis / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice
D016753:Interleukin-10