T H1/T H2-mediated colitis induced by adoptive transfer of CD4 +CD45RB high T lymphocytes into nude mice

Takanori Kanai, Takahiro Kawamura, Taeko Dohi, Shin Makita, Yasuhiro Nemoto, Teruji Totsuka, Mamoru Watanabe

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)89-99
Number of pages11
JournalInflammatory bowel diseases
Volume12
Issue number2
DOIs
Publication statusPublished - 2006 Feb
Externally publishedYes

Keywords

  • Colitis model
  • Crohn's disease
  • Nude mice
  • T 1/T 2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Fingerprint Dive into the research topics of 'T <sub>H</sub>1/T <sub>H</sub>2-mediated colitis induced by adoptive transfer of CD4 <sup>+</sup>CD45RB <sup>high</sup> T lymphocytes into nude mice'. Together they form a unique fingerprint.

Cite this