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Induction of alloreactivity in human adult and umbilical cord blood T cells was evaluated in mixed leukocyte culture by exposure to an allogeneic lymphoblastoid line that expresses known costimulatory molecules. Initial exposure to alloantigen-presenting cells (allo-APC) induced strong proliferative responses in both adult and cord blood T cells. However, in contrast to adult T cells, cord blood T cells exhibited little proliferation after restimulation with donor APC. Primed cord blood T cells could respond to interleukin 2 (IL-2), but unresponsiveness to alloantigen was not overcome by addition of exogenous IL-2. Unresponsiveness was long-lasting and appeared to be maintained by a combination of induction of anergy and activity of CD8+ suppressor cells. This information may contribute to use of human cord blood as an allogeneic source of transplantable stem cells.Experimental and clinical evidence has demonstrated the efficacy of human umbilical cord blood (CB) as a source of transplantable hematopoietic stem and progenitor cells (1-13). More than 60 CB transplants have been performed for treatment of either malignant or nonmalignant diseases in children. The majority have been HLA-matched sibling transplants. Several one-, two-, and three-antigen-mismatched sibling transplants and unrelated matched and partially mismatched transplants have also been performed and were characterized by a relatively low incidence of graft-versus-host disease (GVHD) (2-5, 7-13). These clinical observations led us to evaluate the alloreactive potential of CB T cells. We previously demonstrated that while little cytotoxic T-cell activity was generated after allogeneic stimulation of CB T cells, there was strong cellular proliferation in both adult and CB T cells (14). To determine if this proliferation results in similar qualitative changes in cellular activation/differentiation, we evaluated in vitro proliferative responsiveness of adult and CB T cells following primary alloantigen stimulation.

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Human umbilical cord blood (CB) is being increasingly used both as an alternative to bone marrow to transplant children and for experimental insight into the ontogenic and maturational characteristics of blood cells. We studied the functional and phenotypic characteristics of CB natural killer (NK) cells because of the possibly important role such cells may play in a transplant setting and to gain insight into the little known ontogenic differences and maturational pathways of NK cells. It was found that CB NK lytic activity is usually deficient and that this deficiency cannot be fully explained by the presence of insufficient percentages of CD56+ cells. Although CD16+CD56+ and CD16-CD56+ NK cell subsets typical of adult peripheral blood (PB) are present, a significant population of CD16+CD56- cells also exists in CB. CB CD16+CD56- cells have little or no lytic capabilities; CB CD16+CD56+ cells vary in their lytic capabilities. Although a decreased ability to bind target cells may contribute to the deficient lytic activity of these CB NK cell subsets, studies suggest that other factors must also play a role. Short-term incubation with interleukin-2 (IL-2) or interleukin-12 (IL-12) substantially increases the lytic capabilities of CB NK cells, and long-term incubations induce lymphokine-activated killer (LAK) cell generation. Cell depletion experiments show that activated CD56+ NK cells are responsible for the lytic activity of CB LAK cells. Flow cytometric analysis reveals that during LAK cell generation, CB undergoes phenotypic changes similar to those of PB except that CD16+CD56- cells are still present.(ABSTRACT TRUNCATED AT 250 WORDS)