High IFN-γ production by CD8+ T cells and early sensitization among infants at high risk of atopy

• Published in: Journal of allergy and clinical immunology 2004-04, Vol.113 (4), p.710-716
• Main Authors: Rowe, Julie, Heaton, Tricia, Kusel, Merci, Suriyaarachchi, Devinda, Serralha, Michael, Holt, Barbara J, de Klerk, Nick, Sly, Peter D, Holt, Patrick G
• Format: Article
• Language: English
• Subjects: Allergens - immunology; Atopy; Biological and medical sciences; CD8+ T cells; CD8-Positive T-Lymphocytes - metabolism; Cells, Cultured; cytokines; Cytokines - metabolism; Fetal Blood; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic Predisposition to Disease; Humans; Hypersensitivity - genetics; Immunization; Immunopathology; Infant, Newborn; infants; Interferon-gamma - biosynthesis; Medical sciences; Monocytes - metabolism; Ovalbumin - immunology; Pyroglyphidae - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2003.12.585

High genetic risk (HR) of atopy among unstratified populations of infants is associated with attenuated IFN-γ responses. However, the role of IFN-γ in progression from HR status to active disease is less clear. To identify immune function markers in neonates with HR that are associated with positive atopic outcomes at 2 years. Cord blood mononuclear cells (CBMCs) were collected from 175 children with HR and cryopreserved. The children were assessed for atopy by skin prick at 0.5 and 2 years. CBMCs were thawed and stimulated with allergens and mitogens PHA and staphylococcal enterotoxin B (SEB), and cytokine responses were determined. No correlations were observed between allergen-specific CBMC responses and atopic outcomes. In contrast, sensitization was strongly associated with polyclonal IFN-γ responses to both PHA (P=.002) and SEB (P=.005), and also with SEB-induced IL-5 (P=.05), IL-10 (P=.02), and IL-13 (P=.01). Logistic regression analysis identified elevated PHA-induced IFN-γ and SEB-induced IL-13 responses as the strongest independent predictors of atopy development. Cell separation studies confirmed CD8+ T cells as the source of ∼90% of IFN-γ production. IFN-γ produced by CD8+ T cells may synergize with TH2 cytokines in driving atopy development in children with HR.