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

J Exp Med. 2005 Dec 5;202(11):1549-61. doi: 10.1084/jem.20051506. Epub 2005 Nov 28.

Abstract

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 susceptibility.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antigens, CD / immunology
  • Asthma / immunology*
  • Asthma / pathology
  • Cell Proliferation / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Eosinophilia / immunology
  • Eosinophilia / pathology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Immunoglobulin E / immunology
  • Interleukin-12 / immunology
  • Lung / immunology
  • Lung / pathology
  • Lymphocyte Depletion / methods
  • Mice
  • Mice, Inbred C3H
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Th2 Cells / immunology
  • Th2 Cells / pathology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Interleukin-12
  • Immunoglobulin E