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Am. J. Respir. Crit. Care Med., Volume 164, Number 4, August 2001, 680-687

Role of CD4+ CD25+ Regulatory T Cells in T Helper 2 Cell-mediated Allergic Inflammation in the Airways

AKIRA SUTO, HIROSHI NAKAJIMA, SHIN-ICHIRO KAGAMI, KOTARO SUZUKI, YASUSHI SAITO, and ITSUO IWAMOTO

Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan

It has recently been shown that CD4+ CD25+ T cells are immunoregulatory T cells that prevent CD4+ T cell-mediated organ-specific autoimmune diseases. To determine whether CD4+ CD25+ T cells downregulate Th2 cell-mediated allergic inflammation in the airways, we studied antigen-induced eosinophil recruitment in the airways in BALB/c Rag-2-/- mice transferred with CD4+ CD25+ T cell-depleted or unfractionated T cells from ovalbumin-specific TCR transgenic mice. Antigen-induced eosinophil recruitment into the airways was significantly decreased in the mice transferred with CD4+ CD25+ T cell-depleted splenocytes as compared with those transferred with unfractionated splenocytes. On the other hand, the depletion of CD4+ CD25+ T cells increased antigen-induced neutrophil and T cell recruitment in the airways of the mice. The depletion of CD4+ CD25+ T cells also decreased antigen-induced IL-4 and IL-5 production in the airways of the mice. Finally, the depletion of CD4+ CD25+ T cells prevented antigen-induced Th2 cell differentiation in vitro but increased the differentiation of Th1 cells. These results indicate that CD4+ CD25+ T cells modulate the Th1 and Th2 cell balance toward Th2 cells and thus upregulate Th2 cell-mediated allergic inflammation in the airways.

Keywords: allergic inflammation; eosinophils; CD4+ CD25+ T cells; Th1/Th2 cells




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