Deficient IFN-γ Expression in Umbilical Cord Blood (UCB) T Cells Can Be Rescued by IFN-γ-Mediated Increase in NFATc2 Expression

Regulation of nuclear factor of activated T cells-c2 (NFATc2) gene expression is not clearly defined. We previously reported reduced NFATc2 protein expression in cord blood T lymphocytes. Here we show that NFATc2 expression in T cells is dependent in part on the presence of IFN-γ during primary stimulation, as blocking of IFN-γ blunted NFATc2 protein and mRNA upregulation. Conversely, addition of exogenous IFN-γ during stimulation resulted in increased expression of NFATc2 in cord blood T lymphocytes. This correlated with rescue of deficient IFN-γ expression by cord blood T cells. Rescue of IFN-γ expression in cord blood T cells was dependent on the presence of antigen-presenting cells, as addition of IFN-γ during stimulation of purified cord blood T cells did not result in an increase of IFN-γ expression, and depletion of monocytes ablated the rescue of IFN-γ expression. Our results point to impaired function in the antigen-presenting cell population of cord blood, playing a role in the hyporesponsiveness of T cells.