title: High IFN-gamma production by CD8+ T cells and early sensitization among infants at high risk of atopy.
abstract: BACKGROUND
  High genetic risk (HR) of atopy among unstratified populations of infants is associated with attenuated IFN-gamma responses. However, the role of IFN-gamma in progression from HR status to active disease is less clear.
  
  
  OBJECTIVE
  To identify immune function markers in neonates with HR that are associated with positive atopic outcomes at 2 years.
  
  
  METHODS
  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.
  
  
  RESULTS
  No correlations were observed between allergen-specific CBMC responses and atopic outcomes. In contrast, sensitization was strongly associated with polyclonal IFN-gamma 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-gamma 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 approximately 90% of IFN-gamma production.
  
  
  CONCLUSIONS
  IFN-gamma produced by CD8+ T cells may synergize with T(H)2 cytokines in driving atopy development in children with HR.
authors.affiliation: Telethon Institute for Child Health Research, the University of Western Australia, West Perth, WA 6872, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Rowe
authors.forename: Tricia
authors.initials: T
authors.lastname: Heaton
authors.forename: Merci
authors.initials: M
authors.lastname: Kusel
authors.forename: Devinda
authors.initials: D
authors.lastname: Suriyaarachchi
authors.forename: Michael
authors.initials: M
authors.lastname: Serralha
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Holt
authors.forename: Nick
authors.initials: N
authors.lastname: de Klerk
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D000485:Allergens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood; D020022:Genetic Predisposition to Disease; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007114:Immunization; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis*; D009000:Monocytes / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D007371:Interferon-gamma; D010047:Ovalbumin