TH1/TH2-mediated colitis induced by adoptive transfer of CD4+CD45RBhigh T lymphocytes into nude mice.
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.
Kanai
Takanori
T
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, and the Department of Gastroenterology, Research Institute, International Medical Center of Japan, Tokyo, Japan. taka.gast@tmd.ac.jp
Kawamura
Takahiro
T
Dohi
Taeko
T
Makita
Shin
S
Nemoto
Yasuhiro
Y
Totsuka
Teruji
T
Watanabe
Mamoru
M
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D001707:Biopsy, Needle; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology*; D016207:Cytokines / Q000032:analysis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011336:Probability; D013045:Species Specificity; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019282:Wasting Syndrome / Q000276:immunology / Q000503:physiopathology
D001323:Autoantibodies; D016207:Cytokines; D017493:Leukocyte Common Antigens