Neonatal Cd71+ Erythroid Cells: Immunomodulatory Functions And Role In The Pathogenesis Of Preterm Labor

The neonatal immune system is regulated differently from that of adults, which results in an increased susceptibility to infections and other complications after birth. Preterm neonates in particular are at an extreme risk; however, the mechanisms by which their immune responses are regulated are still poorly understood. One proposed mechanism for the suppression of the neonatal immune system is the presence of nucleated CD71+ erythroid cells. We therefore investigated the presence and function of such cells in the umbilical cord blood of term and preterm neonates. The first aim of this work was to determine the number and frequency of CD71+ erythroid cells in the umbilical cord blood of preterm and term neonates. We found that CD71+ erythroid cells were reduced in the cord blood of neonates born to women who underwent spontaneous preterm labor compared to those who delivered preterm without labor, and that the numbers and frequency of such cells were similar to neonates born to women who delivered at term with or without spontaneous labor. The second aim was to elucidate the functions of CD71+ erythroid cells in the umbilical cord blood of preterm and term neonates. The principle findings of this study were: (1) PTL-derived neonatal CD71+ erythroid cells displayed a similar mRNA profile to that of those from term neonates, and (2) the direct contact, but not soluble products, between preterm or term neonatal CD71+ erythroid cells and maternal mononuclear immune cells induced the release of pro-inflammatory cytokines and a reduction in the release of the anti-inflammatory cytokine TGF-β. Moreover, PTL-derived neonatal CD71+ erythroid cells (3) modestly altered CD8+ T cell activation; (4) inhibited conventional CD4+ and CD8+ T-cell expansion; (5) suppressed the expansion of CD8+ regulatory T cells; (6) regulated cytokine responses mounted by myeloid cells in the presence of a microbial product; and (7) indirectly modulated T-cell cytokine responses. Together, these results demonstrate that neonatal CD71+ erythroid cells have an immunomodulatory, rather than immunosuppressive, function and that these cells are altered in neonates born to women who underwent spontaneous preterm labor