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

Abstract

BACKGROUND:

Transfer of CD4CD45RB 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 CD4CD45RB 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, CD4CD25 T cells were also used.

RESULTS:

Mice reconstituted with CD4CD45RB but not CD4CD25 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 CD4CD45RB and CD4CD45RB did not develop wasting disease or colitis.

CONCLUSIONS:

Collectively, the power of the colitis model induced by the adoptive transfer of CD4CD45RB 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.

• Authors: Takanori Kanai, Takahiro Kawamura, Taeko Dohi, Shin Makita, Yasuhiro Nemoto, Teruji Totsuka, Mamoru Watanabe
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 12 Issue 2 Pg. 89-99 (Feb 2006) ISSN: 1078-0998 [Print] England
• PMID: 16432372 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Cytokines
• Leukocyte Common Antigens

Topics

• Adoptive Transfer (methods)
• Animals
• Autoantibodies (analysis, immunology)
• Autoimmune Diseases (immunology, pathology)
• Biopsy, Needle
• CD4-Positive T-Lymphocytes (immunology, transplantation)
• Colitis, Ulcerative (immunology, pathology)
• Cytokines (analysis, immunology)
• Disease Models, Animal
• Female
• Flow Cytometry
• Immunohistochemistry
• Leukocyte Common Antigens (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Probability
• Species Specificity
• Statistics, Nonparametric
• T-Lymphocyte Subsets (immunology)
• Wasting Syndrome (immunology, physiopathology)