Systemically derived large intestinal CD4+ Th2 cells play a central role in STAT6-mediated allergic diarrhea
Mi-Na Kweon, … , Ichiro Takahashi, Hiroshi Kiyono
Mi-Na Kweon, … , Ichiro Takahashi, Hiroshi Kiyono
Published January 15, 2000
Citation Information: J Clin Invest. 2000;106(2):199-206. https://doi.org/10.1172/JCI8490.
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Article

Systemically derived large intestinal CD4+ Th2 cells play a central role in STAT6-mediated allergic diarrhea

Abstract

Systemically primed BALB/c mice developed severe diarrhea after repeated oral administration of ovalbumin (OVA). Histological analysis demonstrated that dramatic infiltration of eosinophils and mast cells occurred in the large intestine but not in the small intestine of mice with diarrhea. Interestingly, CD4+ αβ T cells of the large intestine secreted IL-4 and IL-13 at high levels. Identically treated STAT6 gene-disrupted mice failed to develop OVA-induced diarrhea. Further, treatment of BALB/c mice with monoclonal anti–IL-4 antibody prevented the development of allergic diarrhea. An adoptive transfer study showed that systemically primed splenic CD4+ T cells were preferentially recruited into the large intestine upon exposure to oral OVA. These results strongly suggest that systemically derived CD4+ αβ T cells of the large intestine play a critical role in the onset of Th2-mediated intestinal allergic disorders via STAT6 signal transduction.

Authors

Mi-Na Kweon, Masafumi Yamamoto, Masahiro Kajiki, Ichiro Takahashi, Hiroshi Kiyono

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Preferential migration of systemically primed splenic GFP+ CD4+ T cells ...
Preferential migration of systemically primed splenic GFP+ CD4+ T cells into large intestines of SCID mice. (a) Migration pattern of GFP+ T cells obtained from the spleen and small and large intestines of SCID mice to which GFP+ CD4+ T cells have been adoptively transferred. (b) Histological analysis of spleen and small and large intestines isolated from recipient SCID mice. Original magnification of ×40 or ×100 was used. (c) Expression of Th1 (IFN-γ) and Th2 (IL-4, IL-5, and IL-13) cytokine–specific mRNA in lymphocytes obtained from the spleen and small and large intestine of recipient SCID mice. (d) Represents the frequency of IFN-γ– and IL-4–secreting cells as determined by intracellular cytokine staining. Representative results from two individual experiments are shown.