Cutting edge:: Chronic intestinal inflammation in STAT-4 transgenic mice:: Characterization of disease and adoptive transfer by TNF- plus IFN-γ-producing CD4+ T cells that respond to bacterial antigens

We generated transgenic mice for STAT-4, a regulatory protein specifically associated with IL-12 signaling, under the control of a CMV promoter, These mice expressed strikingly increased nuclear STAT-4 levels in lamina propria CD4(+) T lymphocytes upon systemic administration of dinitrophenyl-keyhole limpet hemocyanin and developed chronic transmural colitis characterized by infiltrates of mainly CD4(+) T lymphocytes, The latter cells produced predominantly TNF and IFN-gamma but not IL-4 upon activation with alpha CD3/CD28 or autologous bacterial Ags, consistent with a Th1-type cell response, Furthermore, chronic colitis in STAT-4 transgenic mice could be adoptively transferred to SCID mice by colonic and splenic CD4(+) T cells that were activated with Ags from autologous bacterial flora, These data establish a critical molecular signaling pathway involving STAT-4 for the pathogenesis of chronic intestinal inflammation, and targeting of this pathway mag' be relevant for the treatment of colitis in humans.