Maturation of CD4+ Regulatory T Lymphocytes and of Cytokine Secretions in Infants Born Prematurely

Purpose To characterize the maturation of CD4(+) regulatory T lymphocytes (Treg) and of cytokine productions in preterm infants during their first 16 months of life. Methods The proportions of CD4(+) Treg cells, their phenotypic characteristics, and the mitogen-induced cytokine productions by peripheral blood mononuclear cells (PBMC) were analysed in 26 very-preterm infants from 2 to 16 months of age, and compared to results obtained for 17 cord blood mononuclear cells (CBMC) from very-preterm infants, 12 from term infants and to blood samples from 40 adults. Results High proportion of CD25(+/high)CD4(+) Treg cells was found at birth in preterm CB with a gradual decreased afterwards. However, their percentage at 16 months of age was still higher than in term CB. In contrast to adults, preterm infants were characterized by excellent linear correlations between the proportions of CD25(+/high)CD4(+) and CD25(+/high)FoxP3(+) CD4(+) or CD25(+/high)CD127(low) CD4(+) or CD25(+/high)FoxP3+ CD127(low) CD4(+) T lymphocytes. CD45RO(+) and HLA-DR+ expressions were very (low) on preterm Treg and progressively increased with age. Functionally, preterm compared to term CBMC secreted in response to phytohaemagglutinin (low)er IFN-gamma, higher IL-5 and similar IL-12p70, IL-10, IL-2 and IL-13 concentrations. IFN-gamma, IL-12p70 and IL-10 productions were at 16 months still lower than those obtained for adults Conclusion Preterm differed from term CBMC both by their proportion and phenotype of CD4(+) Treg lymphocytes and by their cytokine secretions. Maturation occurred during infancy with similar IFN-gamma secretion but with persistently higher proportion of CD4(+) Treg cells in 1 year preterm infants compared to term neonates.