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

35 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

Fingerprint

Adoptive Transfer
Colitis
Nude Mice
T-Lymphocytes
B-Lymphocytes
Wasting Syndrome
Inflammatory Bowel Diseases
Interleukin-7
Interleukin-5
Regulatory T-Lymphocytes
Interleukin-4
Interleukin-10
Dendritic Cells
Immunoglobulin A
Thymus Gland
Interferons
Hyperplasia
Immunoglobulin M
Colon
Mucous Membrane

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

T H1/T H2-mediated colitis induced by adoptive transfer of CD4 +CD45RB high T lymphocytes into nude mice. / Kanai, Takanori; Kawamura, Takahiro; Dohi, Taeko; Makita, Shin; Nemoto, Yasuhiro; Totsuka, Teruji; Watanabe, Mamoru.

In: Inflammatory Bowel Diseases, Vol. 12, No. 2, 02.2006, p. 89-99.

Research output: Contribution to journalArticle

Kanai, Takanori ; Kawamura, Takahiro ; Dohi, Taeko ; Makita, Shin ; Nemoto, Yasuhiro ; Totsuka, Teruji ; Watanabe, Mamoru. / T H1/T H2-mediated colitis induced by adoptive transfer of CD4 +CD45RB high T lymphocytes into nude mice. In: Inflammatory Bowel Diseases. 2006 ; Vol. 12, No. 2. pp. 89-99.
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AU - Kanai, Takanori

AU - Kawamura, Takahiro

AU - Dohi, Taeko

AU - Makita, Shin

AU - Nemoto, Yasuhiro

AU - Totsuka, Teruji

AU - Watanabe, Mamoru

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AB - 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.

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KW - T 1/T 2

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