Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent.
Deficient suppression of T cell responses to allergen by CD4+CD25+ regulatory T cells has been observed in patients with allergic disease. Our current experiments used a mouse model of airway inflammation to examine the suppressive activity of allergen-specific CD4+CD25+ T cells in vivo. Transfer of ovalbumin (OVA) peptide-specific CD4+CD25+ T cells to OVA-sensitized mice reduced airway hyperreactivity (AHR), recruitment of eosinophils, and T helper type 2 (Th2) cytokine expression in the lung after allergen challenge. This suppression was dependent on interleukin (IL) 10 because increased lung expression of IL-10 was detected after transfer of CD4+CD25+ T cells, and regulation was reversed by anti-IL-10R antibody. However, suppression of AHR, airway inflammation, and increased expression of IL-10 were still observed when CD4+CD25+ T cells from IL-10 gene-deficient mice were transferred. Intracellular cytokine staining confirmed that transfer of CD4+CD25+ T cells induced IL-10 expression in recipient CD4+ T cells, but no increase in IL-10 expression was detected in airway macrophages, dendritic cells, or B cells. These data suggest that CD4+CD25+ T cells can suppress the Th2 cell-driven response to allergen in vivo by an IL-10-dependent mechanism but that IL-10 production by the regulatory T cells themselves is not required for such suppression.
Kearley
Jennifer
J
Leukocyte Biology Section, Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, SW7 2AZ London, England, UK.
Barker
Jane E
JE
Robinson
Douglas S
DS
Lloyd
Clare M
CM
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000276:immunology; D053701:Receptors, Interleukin-10; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10