title: CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function.
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.
authors.affiliation: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Lewkowich
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Herman
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Schleifer
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Dance
authors.forename: Brian L
authors.initials: BL
authors.lastname: Chen
authors.forename: Krista M
authors.initials: KM
authors.lastname: Dienger
authors.forename: Alyssa A
authors.initials: AA
authors.lastname: Sproles
authors.forename: Jaimin S
authors.initials: JS
authors.lastname: Shah
authors.forename: Jörg
authors.initials: J
authors.lastname: Köhl
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018664:Interleukin-12; D007073:Immunoglobulin E