Role of Regulatory T Cells in Noninherited Maternal Antigen-Related Tolerance in Cord Blood: An in Vitro Study

Cord blood (CB) is an alternative stem cell source for allogeneic hematopoietic stem cell transplantation (HSCT). The unique advantages of using CB as a stem cell source are a degree of permissibility for HLA mismatch, rapid availability, and relatively risk-free cell collection. Because HLA is highly polymorphic and population-specific, optimal HLA-matched unrelated donors or cord blood units (CBUs) might not be available. In view of the possibility that matched CBUs that include noninherited maternal antigens (NIMAs) might contain acceptable HLA mismatches, we attempted to determine the degree of alloreactivity of CB mononuclear cells (MNCs) on stimulation by the maternal, paternal, and unrelated stimulator cells. Suppression of T cell proliferation, cytotoxicity, and a cytokine profile indicating suppressed Th1 and elevated IL-10 and TGF-β1 responses were observed in the mixed lymphocyte reaction in response to NIMAs. The increases in IL-10 and TGF-β1 production may be due to the Th2 response and/or regulatory T cells (Tregs). The reduced IL-10 and TGF-β1 production after CD25 depletion could have been due to removal of Tregs from the CB cells. Thus, Tregs appear to play an important role in the CB MNC response to NIMAs, possibly due to the induction of IL-10 and TGF-β1. We hope that our work can provide some evidence of the beneficial effect of NIMAs.