T cells producing the anti‐inflammatory cytokine IL‐10 regulate allergen‐specific Th2 responses in human airways

Abstract

Murine models suggest a critical functional role for the anti-inflammatory cytokine IL-10 in local regulation of allergic airways inflammation. There is little corresponding information on human airway cells. This study aimed to investigate whether local IL-10 production regulates responses by respiratory mucosal leucocytes isolated from nasal polyps. Nasal polyp tissue was harvested from 24 patients sensitised to aeroallergens with chronic rhinitis and polyposis undergoing routine polypectomy. Cells were isolated by matrix proteolysis. Cytokine production by polyp cells was determined by cytometric bead array (CBA) and intracellular cytokine analysis. Surface marker expression by polyp cells was determined by flow cytometry. Allergen stimulation significantly enhanced production of IL-10, but not IL-5 or IFN-γ by nasal polyp cell suspensions. Under the same conditions, neutralisation of IL-10 significantly increased allergen-specific IL-5 and IFN-γ production by nasal polyp cells. Cell depletion experiments showed that T cells themselves were primarily responsible for IL-10 production or for inducing its production by other cells. Intracellular cytokine staining confirmed production of IL-10 in the absence of IL-2 production by T cells in response to allergen. T cells within the human respiratory mucosa produce IL-10, which is capable of inhibiting pro-inflammatory Th2 and Th1 cytokine production in an antigen-specific fashion.