Kinetic Analysis of Phenotypes of Cells and Their Cytokine Expression in the Development of Colitis in Nude Mice with MAIDS Colitis

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LP-BM5 murine leukemia virus is known to induce murine acquired immunodeficiency syndrome (MAIDS). We have shown that adoptively transferred spleen cells of MAIDS mice can induce inflammatory bowel disease (IBD)-like colitis termed "MAIDS colitis" in nude mice. We also reported that the Mac-1^+ macrophages and CD4^+ T cells that produce IFN-γ or IL-10 might play a crucial role in the pathogenesis of MAIDS colitis. To reveal the sequential profiles of the immune response of IBD animal models, we analyzed the kinetics of the phenotype of cells and their cytokine expression in the colon of MAIDS colitis mice. Four-week-old C57BL/6 (B6) mice were inoculated intraperitoneally with LP-BM5 murine leukemia virus (MuLV); 8 weeks after infection, lymph node cells from the mice were transferred into B6 nude mice intraperitoneally to induce MAIDS colitis. Mice were killed every week after cell transfer, and histological and immunohistochemical analyses were performed on their colons. In addition, mRNAs of IFN-γ and IL-10 were detected by RT-PCR, and the protein-expression of these cytokines was detected by double color-staining immunofulorescence analysis. Cellular infiltration into the lamina propria of the colon appeared at week 2,and the number of colon-infiltrating cells gradually increased in MAIDS colitis. These cells were mainly composed of as many CD4^+ T cells as Mac-1^+ ones. Epithelial cell hyperplasia was observed at week 4,but remarkable epithelial cell erosions appeared at week 6. At week 3,mRNA of IL10 expression increased and reached a peak; that of IFN-γ remarkably increased at week 6. From early stages through the late ones, IL-10^+ CD4^+ T cells (Th2) and IFN-γ^+ ones (Th1) coexisted, though the former exceeded the latter. Throughout the development of colitis, Mac-1^+ cells expressed both IFN-γ and IL-10,and the number of both cells was almost equal. In conclusion, the distinct phenotype of macrophages and their kinetics as well as those of CD4^+ Th cells should be considered in the development of MAIDS colitis and IBD.
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