High IFN-gamma production by CD8+ T cells and early sensitization among infants at high risk of atopy.
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.
Rowe
Julie
J
Telethon Institute for Child Health Research, the University of Western Australia, West Perth, WA 6872, Australia.
Heaton
Tricia
T
Kusel
Merci
M
Suriyaarachchi
Devinda
D
Serralha
Michael
M
Holt
Barbara J
BJ
de Klerk
Nick
N
Sly
Peter D
PD
Holt
Patrick G
PG
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
D000485:Allergens; D016207:Cytokines; D007371:Interferon-gamma; D010047:Ovalbumin