Background: The specific mechanisms regulating priming of T-cell immunity to common allergens during early childhood remain to be elucidated, though increasing evidence indicates that antigen-presenting cell function is impaired in childhood.Objective: Examine the relationship between HLA-DR expression on monocytes and B cells, allergen-specific T-cell responses at birth, and clinical outcomes at 2 years of age. Methods: Blood mononuclear cells were obtained from 36 healthy neonates who were followed up clinically to the age of 2 years. Expression of HLA-DR by monocytes and B cells was determined at baseline and after in vitro exposure to IFN-gamma, a cytokine that is known to upregulate the expression of HLA-DR. Mononuclear cells were stimulated with endotoxin or a panel of inhalant and food allergens, and cytokine responses and lymphoproliferation were determined after 1 and 5 days, respectively.Results: The magnitude of HLA-DR upregulation on IFN-gamma-stimulated cord blood CD14(+) monocytes was consistently correlated with allergen-induced, but not mitogen-induced, lymphoproliferation at birth. HLA-DR upregulation on monocytes was also positively associated with endotoxin-induced IL-12 p70 synthesis (tau = 0.46; P < .001) but inversely related to mite- and ovalbumin-induced IL-13 synthesis (P = .0006 and P < .003, respectively). HLA-DR expression on unstimulated cord blood monocytes was inversely associated with symptoms of atopic disease at the 2-year follow-up (P = .015). In contrast, HLA-DR expression on B cells was not associated with these parameters of immune function.Conclusions: These findings suggest that the maturity of neonatal monocytes and their responsiveness to external stimuli are linked to differing patterns of immune reactivity at birth and to the risk of allergic symptoms in early childhood.