Alloreactivity of umbilical cord blood mononuclear cells: specific hyporesponse to noninherited maternal antigens

Earlier studies noted that patients who underwent cord blood (CB) transplantation had a lower incidence of graft-versus-host disease (GVHD) than those who underwent bone marrow transplantation (BMT). The premise that the immune reactivity of CB mononuclear cells (CB-MNC) to HLA mismatched combinations and to noninherited maternal antigens (NIMA) may be one of the factors involved in this phenomenon is still debatable. In this study we have attempted to evaluate the alloresponse and alloreactivity induced by CB-MNC by means of the standard mixed lymphocyte reaction test (SMLR) and the more sensitive, modified mixed lymphocyte reaction test (MMLR). Both techniques were used to test CB-MNC (n = 28) against HLA class II mismatched MNC from mothers (n = 26), fathers (n = 12), and unrelated individuals (n = 60) who served as controls. Alloresponse capabilities and stimulation capacities of CB-MNC in the SMLR were similar to those of control MNC: relative response (RR) = 73 vs. 65 and 58 vs. 65, respectively. Similar results were obtained in the MMLR. CB-MNC responded weakly to the maternal MNC in comparison with control MNC (RR = 47 vs. 73 [p = 0.0099]), while a stronger response was noted to the paternal than the maternal MNC (RR = 72 vs. 47 [p = 0.045]). Our results demonstrate that CB-MNC both respond to and induce alloresponse in HLA mismatched combinations. Moreover, the hyporesponse of CB-MNC to maternal cells that we observed suggests a form of tolerance to NIMA, which is probably due to the fetus's exposure to these antigens in its intrauterine life.