Graft-Versus-Host Disease and Graft-Versus-Leukemia Effect in Mice Grafted With Peripheral Newborn Blood

We previously used peripheral newborn blood (NBB) as a possible invivo experimental model for cord blood (CB) transplantation and showedthat B10.D2 NBB cells successfully reconstituted adult (DBA/2 × B10.D2)F1 mice without causing graft-versus-host disease (GVHD),probably because of their phenotypic and functional immaturity. Here weinvestigated the influence of T-cell maturation occurring in NBB cellsduring the early postbirth period on the degree of engraftment, theincidence of GVHD, and the graft-versus-leukemia (GVL) potential. Theseparameters were compared in recipients grafted with bone marrow (BM)cells. We observed an increased percentage of CD4⁺ matureT cells accompanied by the acquisition of proliferative responses tophytohemagglutinin (PHA) and to allogeneic cells of day-5 NBB cells.The capacity of day-2 NBB to engraft was moderately reduced andrecipients developing GVHD were occasionally observed after the graftof day-5 NBB cells. No GVL effect was evidenced regardless of the timeof postbirth blood collection. However, the GVL effect can be obtainedby the delayed infusion of donor mature T cells to recipients graftedwith day-0 NBB, without causing GVHD. In contrast, the same protocolapplied to mice grafted with BM cells induced GVHD mortality of allrecipients. Interleukin (IL)-10 but not IL-2 messenger RNA wasexpressed in NBB cells as opposed to BM cells. These findings suggestthat, in terms of GVHD incidence, delayed infusion of mature T cells aspost-transplant tumor immunotherapy would be more effective whenapplied after CB than after BM transplantation.