| First Author | Davidson NJ | Year | 1998 |
| Journal | J Immunol | Volume | 161 |
| Issue | 6 | Pages | 3143-9 |
| PubMed ID | 9743382 | Mgi Jnum | J:112240 |
| Mgi Id | MGI:3655904 | Doi | 10.4049/jimmunol.161.6.3143 |
| Citation | Davidson NJ, et al. (1998) IL-12, but not IFN-gamma, plays a major role in sustaining the chronic phase of colitis in IL-10-deficient mice. J Immunol 161(6):3143-9 |
| abstractText | IL-10-deficient (IL-10(-/-)) mice develop chronic enterocolitis mediated by CD4+ Th1 cells producing IFN-gamma. Because IL-12 can promote Th1 development and IFN-gamma production, the ability of neutralizing anti-IL-12 mAb to modulate colitis in IL-10(-/-) mice was investigated. Anti-IL-12 mAb treatment completely prevented disease development in young IL-10(-/-) mice. Treatment of adult mice resulted in significant amelioration of established disease accompanied by reduced numbers of mesenteric lymph node and colonic CD4+ T cells and of mesenteric lymph node T cells spontaneously producing IFN-gamma. In contrast, anti-IFN-gamma mAb had minimal effect on disease reversal, despite a significant preventative effect in young mice. These findings suggested that IL-12 sustains colitis by supporting the expansion of differentiated Th1 cells that mediate disease independently of their IFN-gamma production. This conclusion was supported by the finding that anti-IL-12 mAb greatly diminished the ability of a limited number of CD4+ T cells expressing high levels of CD45RB from diseased IL-10(-/-) mice to expand and cause colitis in recombination-activating gene-2(-/-) recipients, while anti-IFN-gamma mAb had no effect. Furthermore, IL-12 could support pathogenic IL-10(-/-) T cells stimulated in vitro in the absence of IL-2. While these studies show that IL-12 plays an important role in sustaining activated Th1 cells during the chronic phase of disease, the inability of anti-IL-12 mAb to abolish established colitis or completely prevent disease transfer by Thl cells suggests that additional factors contribute to disease maintenance. |
