ANALYSIS OF THE ALLOREACTIVE CAPACITY OF HUMAN UMBILICAL-CORD BLOOD -IMPLICATIONS FOR GRAFT-VERSUS-HOST DISEASE

Hematopoietic reconstitution by bone marrow transplantation (BMT) is u sed as therapy for the treatment of various malignancies and genetic b lood disorders. Allogeneic BMT is the most common application of this treatment but is frequently associated with graft-versus-host disease (GVHD). Recent clinical studies have shown that sibling transplant usi ng umbilical cord blood (UCB) is an acceptable alternative to BMT and may involve fewer problems with GVHD. We have investigated the in vitr o alloreactive capacity of UCB as it relates to allogeneic transplanta tion. Initial screening assays demonstrated that UCB T cells were func tionally immature. It was not possible to generate significant levels of alloantigen-specific cytotoxic T lymphocytes (CTL) in either primar y or secondary mixed lymphocyte cultures. Limiting dilution analyses r evealed that cord blood T cells were 10-1000 X less alloreactive in te rms of proliferative T cells (PTLp) and cytotoxic T cells (CTLp) compa red with adult peripheral blood lymphocytes (PBL). However, UCB was eq uivalent to adult PBL in terms of natural killer (NK) and lymphokine-a ctivated kilter (LAK) cell precursors. Analysis of cells from alloanti gen-stimulated MLC revealed that UCB generated primarily CD4(+) and CD 16(+) cells that made little or no IL-4, IL-6, TNF-alpha or IFN-gamma on antigenic stimulation. Cold target inhibition analyses revealed tha t alloantigen-stimulated cord blood T cells had a fine specificity sim ilar to NK cells. From these in vitro results cord blood would seem to be unlikely to mediate severe GVHD reactions in vivo and should be su itable for allogeneic transplantation.