Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells

Background: Levels of the Clara cell 16-kd protein (CC16) are lower in plasma and bronchoalveolar lavage fluid from adults with asthma relative to those seen in healthy control subjects, and CC16 inhibits the T(H)2 cytokine production from marine T cells. Objective: We sought to determine the plasma levels of CC16 in infants and to investigate whether CC16 might inhibit the T(H)2 cytokine production from neonatal T cells. Methods: Cord blood and blood samples at 4, 18, and 36 months of age were taken from 64 children prospectively, and CC16 levels were analyzed in plasma. Cord monocyte-derived dendritic cells (DCs) were pulsed with birch allergen extract alone or together with CC16 or prostaglandin D-2 receptor inhibitors, after which autologous naive CD4(+) T cells were added to the DCs. The production of IL-5, IL-13, and IFN-gamma was measured by means of ELISA and flow cytometry. Results: The plasma levels of CC16 in children peaked at 4 months. CC16 did not directly affect the cytokine production from human T(H)2 cells. However, CC16 inhibited birch pollen extract-stimulated T(H)2 differentiation of naive T cells through the DC. Inhibition of the prostaglandin D-2 receptors did not consistently result in suppressed T(H)2 differentiation. Conclusion: The production of CC16 seems to peak early in life, and CC16 has an inhibitory effect on T(H)2 cell differentiation from human infants by affecting DCs. Clinical implications: CC16 is an immunoregulatory protein, and its inhibitory effect on T(H)2 cell differentiation might be of importance in the pathogenesis of allergy in infants.