Mechanisms of asthma and allergic inflammation
Clara cell 16-kd protein downregulates TH2 differentiation of human naive neonatal T cells

https://doi.org/10.1016/j.jaci.2007.03.021Get rights and content

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 TH2 cytokine production from murine T cells.

Objective

We sought to determine the plasma levels of CC16 in infants and to investigate whether CC16 might inhibit the TH2 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 D2 receptor inhibitors, after which autologous naive CD4+ T cells were added to the DCs. The production of IL-5, IL-13, and IFN-γ 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 TH2 cells. However, CC16 inhibited birch pollen extract–stimulated TH2 differentiation of naive T cells through the DC. Inhibition of the prostaglandin D2 receptors did not consistently result in suppressed TH2 differentiation.

Conclusion

The production of CC16 seems to peak early in life, and CC16 has an inhibitory effect on TH2 cell differentiation from human infants by affecting DCs.

Clinical implications

CC16 is an immunoregulatory protein, and its inhibitory effect on TH2 cell differentiation might be of importance in the pathogenesis of allergy in infants.

Section snippets

Subjects

Sixty-four healthy Swedish infants born in 2001-2003 at the Sahlgrenska University Hospital (Göteborg, Sweden) were involved in the study. These children formed part of a prospective birth cohort study (IMMUNOFLORA). Inclusion criteria were normal pregnancy without expected complications and expected vaginal delivery at term (at least 38 weeks' gestational age). The parental history of allergy was recorded. Blood samples were collected from the umbilical cord and at 4, 18, and 36 months of age,

Levels of CC16 peaked in infants at 4 months of age

To investigate the levels of CC16 in children during the first years of life, we measured the concentrations of CC16 in plasma in cord blood and at 4 and 18 months and 3 years from a cohort of children. The levels of CC16 increased significantly from a median level of 15 ng/mL at birth to a level of 96 ng/mL at the age of 4 months (Fig 1). Thereafter, the levels of CC16 decreased significantly to 20 ng/mL at 18 months and continued to decrease to 7 ng/mL at the age of 3 years. The CC16 levels

Discussion

Previous studies show that the levels of CC16 are lower in asthmatic patients compared with those seen in healthy control subjects. However, it is still not clear whether these differences in CC16 levels have an effect on the immunopathogenic mechanisms of allergic inflammation. In the present study we investigated the levels of CC16 in blood during the first 3 years of life and whether CC16 might have an opportunity to affect T-cell development of children in vitro. We unexpectedly found that

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Supported by the Swedish Research Council, the Vårdal Foundation, Cancer-och Allergifonden, the Sahlgrenska Academy at Göteborg University, the Swedish Asthma and Allergy Association Research Foundation, Frimurare Barnhusdirektionen, Åke Wibergs stiftelse, and Konsul Th. C. Berghs stiftelse.

Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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