Cellular alloreactivity of human cord blood cells detected by T-cell frequency analysis and a human skin explant model

Recent clinical data have demonstrated the success of allogeneic stem cell transplantation using HLA-mismatched unrelated human umbilical cord blood (CB). The incidence and severity of acute graft-versus-host disease (GVHD) in these mainly pediatric transplants is low. The immunological mechanisms by which CB transplants may result in reduced GVHD is not completely clear. In this study, the functional cellular alloreactivity of CB cells was investigated, by measuring the frequency of alloreactive helper and cytotoxic T lymphocyte precursors (HTLp and CTLp, respectively) in CB and detecting the ability of CB cells to induce graft-versus-host (GVH) type alloreactivity in vitro. A human skin explant model was used to measure GVH type alloreactivity in vitro. A combined limiting dilution assay was carried out in parallel to determine alloreactive HTLp and CTLp frequencies. The cellular alloreactivity was compared between cord and HLA-haploidentical parental blood cells against the same HLA-mismatched unrelated stimulator. The results demonstrated that alloreactive CTLp frequency in CB mononuclear cells (CBMCs) was significantly lower (mean, 1:35,694, range, 1:1,667-