CD4 + CD25 + T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function

作者：Ian Lewkowich, Nancy Herman, Kathleen W. Schleifer, Matthew P. Dance, Brian L. Chen, Krista Dienger, Alyssa Sproles, Jaimin S. Shah, Jörg Köhl, Yasmine Belkaid, Marsha Wills‐Karp · 发表于：The Journal of Experimental Medicine · 年份：2005 · DOI：10.1084/jem.20051506 · 被引用次数：397 · 研究领域：T-cell and B-cell Immunology、Asthma and respiratory diseases、Immune Cell Function and Interaction

The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25-mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell-depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell-depleted C3H mice. T reg cell-depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell-depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibilit...