TH1/TH2-mediated colitis induced by adoptive transfer of CD4+CD45RBhigh T lymphocytes into nude mice.
Kanai, Takanori MD, PhD 1,*; Kawamura, Takahiro MD, PhD 1; Dohi, Taeko MD, PhD 2; Makita, Shin MD, PhD 1; Nemoto, Yasuhiro MD 1; Totsuka, Teruji MD, PhD 1; Watanabe, Mamoru MD, PhD 1
Inflammatory Bowel Diseases.
12(2):89-99, February 2006.
(Format: HTML, PDF)
Background: Transfer of CD4 CD45RBhigh T cells from normal donors to SCID/Rag-1, 2-deficient mice, which lack T and B cells, leads to the development of a TH1-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 CD45RBhigh 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 CD45RBhigh 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-[gamma], tumor necrosis factor-[alpha], 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 CD45RBhigh and CD4 CD45RBlow did not develop wasting disease or colitis.
Conclusions: Collectively, the power of the colitis model induced by the adoptive transfer of CD4 CD45RBhigh T cells into nude mice is that one can investigate the roles of TH2-type cells and B cells in a regulatory T cell-depleted condition.
(C) Crohn's & Colitis Foundation of America, Inc.