T _H1/T _H2-mediated colitis induced by adoptive transfer of CD4 ⁺CD45RB ^high T lymphocytes into nude mice

Background: Transfer of CD4 ⁺CD45RB ^high T cells from normal donors to SCID/Rag-1, 2-deficient mice, which lack T and B cells, leads to the development of a T _H1-mediated inflammatory bowel disease (IBD)-like syndrome characterized by extensive mononuclear cell infiltrates and epithelial cell hyperplasia. Because it is well known that B cells are also involved in a multitude of mechanistic pathways in human IBD, this study attempts to establish a new model of colitis in nude mice. Methods: We transferred CD4 ⁺CD45RB ^high T cells into athymic nude mice, which lack thymus-dependent T cells but retain normal B cells, to establish and investigate a B cell-involving chronic colitis model. As a control, CD4 ⁺CD25 ^- T cells were also used. Results: Mice reconstituted with CD4 ⁺CD45RB ^high but not CD4 ⁺CD25 ^- T cells developed a wasting disease, with severe infiltrates of B cell aggregates as well as T cells, macrophages, and dendritic cells into the colon and elevated levels of interferon-γ, tumor necrosis factor-α, interleukin (IL)-4, IL-5, and IL-10, by 7 weeks after T cell transfer. Furthermore, the infiltrated lamina propria B cells in colitic nude mice consisted predominantly of massive aggregated immunoglobulin (Ig) M- and scattered IgG-positive cells, but not IgA-positive cells. In contrast, mice reconstituted with CD4 ⁺CD45RB ^high and CD4 ⁺CD45RB ^low did not develop wasting disease or colitis. Conclusions: Collectively, the power of the colitis model induced by the adoptive transfer of CD4 ⁺CD45RB ^high T cells into nude mice is that one can investigate the roles of T _H2-type cells and B cells in a regulatory T cell-depleted condition.