Inflammatory Bowel Diseases

Skip Navigation LinksHome > February 2006 - Volume 12 - Issue 2 > TH1/TH2‐mediated colitis induced by adoptive transfer of CD4...
Inflammatory Bowel Diseases:
doi: 10.1097/01.MIB.0000197237.21387.mL
Original Articles

TH1/TH2‐mediated colitis induced by adoptive transfer of CD4+CD45RBhigh T lymphocytes into nude mice

Kanai, Takanori MD, PhD1,*; Kawamura, Takahiro MD, PhD1; Dohi, Taeko MD, PhD2; Makita, Shin MD, PhD1; Nemoto, Yasuhiro MD1; Totsuka, Teruji MD, PhD1; Watanabe, Mamoru MD, PhD1

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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‐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+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.

© Crohn's & Colitis Foundation of America, Inc.

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