Umbilical cord blood contains normal frequencies of cytotoxic T-lymphocyte precursors (ctlp) and helper T-lymphocyte precursors against noninherited maternal antigens and noninherited paternal antigens

Abstract

 Umbilical cord blood (UCB) has been successfully used as an alternative source of hematopoietic stem cells for allogeneic transplantation. A relatively low incidence and severity of graft-versus-host disease (GVHD) following UCB transplants has been reported, and it has been suggested that this may be caused by a low frequency of alloreactive lymphocytes in UCB. Low frequencies of alloreactive T lymphocytes in UCB may allow transplantation across major MHC barriers with an acceptable risk of GVHD. We investigated cytotoxic T-lymphocyte precursor (CTLp) and helper T-lymphocyte precursor (HTLp) frequencies in UCB. Normal frequencies of CTLp and HTLp were measured against 1–2 HLA class I and 0–1 HLA-DR mismatched stimulator cells. Since it has been postulated that due to maternal fetal transfusion during pregnancy, fetal blood lymphocytes may become tolerant for noninherited maternal antigens (NIMA), allowing transplantation over certain HLA barriers, reactivity of 24 umbilical cord blood samples was analyzed against both parents. The median frequencies of CTLp against NIMA with 1 class-I mismatch was 79 per 10⁶ nucleated cells (range 16–428) and with 2 class I mismatches 121 (range 33–748). CTLp frequencies against noninherited paternal antigens (NIPA) were not statistically different from those against NIMA, with a median of 115 (range 8–336) and 176 (range 50–725) for 1 or 2 HLA class I mismatches, respectively. HTLp frequencies in UCB against parents with 0 or 1 HLA-DR antigen mismatches were similar with respect to NIMA (median 74, range 43–233 and 88, range 16–777, respectively) and NIPA (median 125, range 18–174, and 110, range 28–350, respectively). In four cases, UCB from two HLA-identical siblings was tested against both parents. A correlation between the frequencies of CTLp and HTLp from HLA-identical individuals was found, illustrating that these frequencies are genetically determined. These results illustrate that UCB contains normal frequencies of CTLp and HTLp against MHC alloantigens.