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Alteration of interleukin 4 production results in the inhibition of T helper type 2 cell-dominated inflammatory bowel disease in T cell receptor alpha chain-deficient mice.

Iijima H, Takahashi I, Kishi D, Kim JK, Kawano S, Hori M, Kiyono H - J. Exp. Med. (1999)

Bottom Line: The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4(+)TCR-betabeta (CD4(+)betabeta) T cells producing predominantly interleukin (IL)-4.Although TCR-alpha(-/-) mice treated with either specific or mock Ab developed CD4(+)betabeta T cells, only those treated with anti-IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon gamma-specific expression.These findings suggest that IL-4-producing Th2-type CD4(+)betabeta T cells play a major immunopathological role in the induction of IBD in TCR-alpha(-/-) mice, a role that anti-IL-4 mAb inhibits by causing Th2-type CD4(+)betabeta T cells to shift to the Th1 type.

View Article: PubMed Central - PubMed

Affiliation: Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Japan.

ABSTRACT
T cell receptor alpha chain-deficient (TCR-alpha(-/-)) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4(+)TCR-betabeta (CD4(+)betabeta) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4(+)betabeta T cells, we treated TCR-alpha(-/-) mice with anti-IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-alpha(-/-) mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti-IL-4 mAb-treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab-treated mice. Although TCR-alpha(-/-) mice treated with either specific or mock Ab developed CD4(+)betabeta T cells, only those treated with anti-IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon gamma-specific expression. These findings suggest that IL-4-producing Th2-type CD4(+)betabeta T cells play a major immunopathological role in the induction of IBD in TCR-alpha(-/-) mice, a role that anti-IL-4 mAb inhibits by causing Th2-type CD4(+)betabeta T cells to shift to the Th1 type.

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Enumeration of Ab-producing cells in systemic and mucosal lymphoid tissues from mice treated with anti–IL-4 mAb (hatched bars) or mock Ab (black bars). Mononuclear cells isolated from SP, MLNs, and colonic LP (LPL) of TCR-α−/− mice treated with anti–IL-4 mAb or rat IgG2b (mock Ab) were examined by isotype-specific ELISPOT. Data represent the mean ± SEM from five mice per group of three separate experiments. *Significantly different from each other (P < 0.01) by Student's t test.
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Figure 2: Enumeration of Ab-producing cells in systemic and mucosal lymphoid tissues from mice treated with anti–IL-4 mAb (hatched bars) or mock Ab (black bars). Mononuclear cells isolated from SP, MLNs, and colonic LP (LPL) of TCR-α−/− mice treated with anti–IL-4 mAb or rat IgG2b (mock Ab) were examined by isotype-specific ELISPOT. Data represent the mean ± SEM from five mice per group of three separate experiments. *Significantly different from each other (P < 0.01) by Student's t test.

Mentions: To further confirm the reduction of Ab production at the cellular base, mononuclear cells were isolated from systemic and mucosal tissues of TCR-α−/− mice treated with anti–IL-4 mAb and mock Ab for subsequent ELISPOT assay. The numbers of Ab-forming cells were increased in the systemic lymphoid (e.g., SP) as well as in mucosa-associated tissues (e.g., MLNs, colonic LP) of TCR-α−/− mice treated with mock Ab (Fig. 2). On the other hand, numbers of IgA, IgG, and IgM Ab–forming cells from TCR-α−/− mice treated with anti–IL-4 mAb were significantly decreased both in the systemic lymphoid and mucosa-associated tissues (P < 0.01; Fig. 2).


Alteration of interleukin 4 production results in the inhibition of T helper type 2 cell-dominated inflammatory bowel disease in T cell receptor alpha chain-deficient mice.

Iijima H, Takahashi I, Kishi D, Kim JK, Kawano S, Hori M, Kiyono H - J. Exp. Med. (1999)

Enumeration of Ab-producing cells in systemic and mucosal lymphoid tissues from mice treated with anti–IL-4 mAb (hatched bars) or mock Ab (black bars). Mononuclear cells isolated from SP, MLNs, and colonic LP (LPL) of TCR-α−/− mice treated with anti–IL-4 mAb or rat IgG2b (mock Ab) were examined by isotype-specific ELISPOT. Data represent the mean ± SEM from five mice per group of three separate experiments. *Significantly different from each other (P < 0.01) by Student's t test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195615&req=5

Figure 2: Enumeration of Ab-producing cells in systemic and mucosal lymphoid tissues from mice treated with anti–IL-4 mAb (hatched bars) or mock Ab (black bars). Mononuclear cells isolated from SP, MLNs, and colonic LP (LPL) of TCR-α−/− mice treated with anti–IL-4 mAb or rat IgG2b (mock Ab) were examined by isotype-specific ELISPOT. Data represent the mean ± SEM from five mice per group of three separate experiments. *Significantly different from each other (P < 0.01) by Student's t test.
Mentions: To further confirm the reduction of Ab production at the cellular base, mononuclear cells were isolated from systemic and mucosal tissues of TCR-α−/− mice treated with anti–IL-4 mAb and mock Ab for subsequent ELISPOT assay. The numbers of Ab-forming cells were increased in the systemic lymphoid (e.g., SP) as well as in mucosa-associated tissues (e.g., MLNs, colonic LP) of TCR-α−/− mice treated with mock Ab (Fig. 2). On the other hand, numbers of IgA, IgG, and IgM Ab–forming cells from TCR-α−/− mice treated with anti–IL-4 mAb were significantly decreased both in the systemic lymphoid and mucosa-associated tissues (P < 0.01; Fig. 2).

Bottom Line: The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4(+)TCR-betabeta (CD4(+)betabeta) T cells producing predominantly interleukin (IL)-4.Although TCR-alpha(-/-) mice treated with either specific or mock Ab developed CD4(+)betabeta T cells, only those treated with anti-IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon gamma-specific expression.These findings suggest that IL-4-producing Th2-type CD4(+)betabeta T cells play a major immunopathological role in the induction of IBD in TCR-alpha(-/-) mice, a role that anti-IL-4 mAb inhibits by causing Th2-type CD4(+)betabeta T cells to shift to the Th1 type.

View Article: PubMed Central - PubMed

Affiliation: Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Japan.

ABSTRACT
T cell receptor alpha chain-deficient (TCR-alpha(-/-)) mice are known to spontaneously develop inflammatory bowel disease (IBD). The colitis that develops in these mice is associated with increased numbers of T helper cell (Th)2-type CD4(+)TCR-betabeta (CD4(+)betabeta) T cells producing predominantly interleukin (IL)-4. To investigate the role of these Th2-type CD4(+)betabeta T cells, we treated TCR-alpha(-/-) mice with anti-IL-4 monoclonal antibody (mAb). Approximately 60% of TCR-alpha(-/-) mice, including those treated with mock Ab and those left untreated, spontaneously developed IBD. However, anti-IL-4 mAb-treated mice exhibited no clinical or histological signs of IBD, and their levels of mucosal and systemic Ab responses were lower than those of mock Ab-treated mice. Although TCR-alpha(-/-) mice treated with either specific or mock Ab developed CD4(+)betabeta T cells, only those treated with anti-IL-4 mAb showed a decrease in Th2-type cytokine production at the level of mRNA and protein and an increase in interferon gamma-specific expression. These findings suggest that IL-4-producing Th2-type CD4(+)betabeta T cells play a major immunopathological role in the induction of IBD in TCR-alpha(-/-) mice, a role that anti-IL-4 mAb inhibits by causing Th2-type CD4(+)betabeta T cells to shift to the Th1 type.

Show MeSH
Related in: MedlinePlus