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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.To investigate the role of these Th2-type CD4(+)betabeta T cells, we treated TCR-alpha(-/-) mice with anti-IL-4 monoclonal antibody (mAb).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.

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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Related in: MedlinePlus

Comparison of Ig levels in serum and fecal extracts of TCR-α−/− mice treated with anti–IL-4 mAb (hatched bars) or rat IgG2b (mock Ab, black bars). (A) The levels of IgA, IgG, and IgM Abs in serum and fecal extracts were analyzed by ELISA. (B) The levels of IgG subclass Ab were also analyzed by ELISA. Data represent the mean ± SEM from eight mice per group. *Significantly different from each other (P < 0.01) by Student's t test.
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Figure 1: Comparison of Ig levels in serum and fecal extracts of TCR-α−/− mice treated with anti–IL-4 mAb (hatched bars) or rat IgG2b (mock Ab, black bars). (A) The levels of IgA, IgG, and IgM Abs in serum and fecal extracts were analyzed by ELISA. (B) The levels of IgG subclass Ab were also analyzed by ELISA. Data represent the mean ± SEM from eight mice per group. *Significantly different from each other (P < 0.01) by Student's t test.

Mentions: As increased levels of Abs are one of the immunological features of TCR-α−/− mice with IBD 10, we sought to determine and compare the levels of serum and fecal IgA, IgG, and IgM Abs in anti–IL-4 mAb– and mock Ab–treated TCR-α−/− mice at 25 wk of age by using ELISA. Serum as well as fecal Ab titers were increased in mock Ab–treated TCR-α−/− mice (Fig. 1 A). The levels of Ab titers in these mice were comparable to those of untreated mice, as observed in previous reports 910. However, the levels of IgA, IgG, and IgM Abs in serum and fecal extracts were significantly decreased in TCR-α−/− mice treated with anti–IL-4 mAb (P < 0.01; Fig. 1 A). When IgG subclass Ab titers of TCR-α−/− mice treated with anti–IL-4 mAb were examined by ELISA, levels of IgG1 and IgG2b were found to have decreased and those of IgG2a to have increased significantly (P < 0.01; Fig. 1 B).


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)

Comparison of Ig levels in serum and fecal extracts of TCR-α−/− mice treated with anti–IL-4 mAb (hatched bars) or rat IgG2b (mock Ab, black bars). (A) The levels of IgA, IgG, and IgM Abs in serum and fecal extracts were analyzed by ELISA. (B) The levels of IgG subclass Ab were also analyzed by ELISA. Data represent the mean ± SEM from eight mice per group. *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 1: Comparison of Ig levels in serum and fecal extracts of TCR-α−/− mice treated with anti–IL-4 mAb (hatched bars) or rat IgG2b (mock Ab, black bars). (A) The levels of IgA, IgG, and IgM Abs in serum and fecal extracts were analyzed by ELISA. (B) The levels of IgG subclass Ab were also analyzed by ELISA. Data represent the mean ± SEM from eight mice per group. *Significantly different from each other (P < 0.01) by Student's t test.
Mentions: As increased levels of Abs are one of the immunological features of TCR-α−/− mice with IBD 10, we sought to determine and compare the levels of serum and fecal IgA, IgG, and IgM Abs in anti–IL-4 mAb– and mock Ab–treated TCR-α−/− mice at 25 wk of age by using ELISA. Serum as well as fecal Ab titers were increased in mock Ab–treated TCR-α−/− mice (Fig. 1 A). The levels of Ab titers in these mice were comparable to those of untreated mice, as observed in previous reports 910. However, the levels of IgA, IgG, and IgM Abs in serum and fecal extracts were significantly decreased in TCR-α−/− mice treated with anti–IL-4 mAb (P < 0.01; Fig. 1 A). When IgG subclass Ab titers of TCR-α−/− mice treated with anti–IL-4 mAb were examined by ELISA, levels of IgG1 and IgG2b were found to have decreased and those of IgG2a to have increased significantly (P < 0.01; Fig. 1 B).

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.To investigate the role of these Th2-type CD4(+)betabeta T cells, we treated TCR-alpha(-/-) mice with anti-IL-4 monoclonal antibody (mAb).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.

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