Analysis of the pathogenesis of inflammatory bowel disease using experimental colitis induced by a murine retrovirus

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BACKGROUND : LP-BM5 murine leukemia virus (MuLV) is known to induce murine AIDS (MAIDS). We have shown that sjogren's syndrome (SjS) -like exocrinopathy can be induced in mice with MAIDS and that adoptive transfer of spleen cells from MAIDS mice can induce inflammatory bowel disease-like colitis as well as SjS-like exocrinopathy in nude mice. AIM : To assess the role of interferon (IFN)-g and interleukin (IL)-10 in the pathogenesis of our experimental model, we tried to identify the cells producing these cytokines and their localization in the colitis lesions in situ. METHODS : Four-week-old C57BL/6 (B6) mice were inoculated intraperitoneally with LP-BM5 MuLV.Eight weeks after infection, lymph node cells prepared from the virus-infected mice were transferred to B6 nude mice. Four to six weeks after the cell transfer, mice with clinical symptoms such as diarrhea, anal bleeding and body weight loss were killed to examine their colons. Expression of mRNA for IFN-g and IL-10 was assessed b … More y RTPCR, and protein expression of these cytokines was also analyzed in frozen sections of colon by double color-staining immunofluorescence (IF). RESULTS : All of the mice inoculated with MAIDS lymph node cells showed colitis as well as systemic exocrinopathy, and died within 6 weeks after cell transfer. Scattered erosions of the colon were observed. CD4+ cells were dominant and distributed diffusely within the mucosal and submucosal layers. A few CD8+ cells were detected among the intraepithelial lymphocytes of the colon. Mac-1+ cells were usually localized diffusely within the lamina propria and characteristically detected beneath the injured epithelial cells. B220+cells were localized within lymph follicles. An increase of IFN- g and IL-10 mRNA was detected in the colon of mice with colitis, but not in that of control mice. Double color IF showed that Mac-1+ cells were positive for IFN-g or IL-10 and that most CD4+ cells were positive for IL-10, although the population of IFN-g-positive CD4+ cells was low.CONCLUSIONS : In our experimental colitis model, Mac-1+ macrophages which produce both IFN-g and IL-10 might play a crucial role in the pathogenesis of colitis in combination with CD4+ T cells. Less