NK cells recover early and mediate cytotoxicity via perforin/granzyme and Fas/FasL pathways in umbilical cord blood recipients

Umbilical cord blood (UCB) is now widely accepted as a source of stem cells in patients with malignant hematologic and genetic disorders. We have rece ntly reported that in a series of 30 pediatric UCB transplant recipients co mparable outcome to that anticipated with other unrelated stern cell source s. In our series, however, the probability of GVHD for grade III-IV was 9% and no UCB recipient developed chronic GVHD. The reason for the low inciden ce of GVHD after UCB transplantation is not fully understood. Because funct ional NK cells are among the first population of lymphocytes to be detected in UCB transplant recipients, 2 months post-transplant on average, we want ed to establish whether NK cells could be implicated in reducing the risk o f GVHD. Here, we confirm that early NK cells detected in UCB transplant rec ipients activate the granzyme/perforin lyric pathway and, in addition, they can mediate Fas/Fas ligand (FasL) activity, a Finding not previously repor ted. Both pathways develop simultaneously and are detectable months before the other lymphocytes, notably CD8 are fully functional. Our contention, th erefore, is that the low GVHD observed in UCB recipients may be partially d ue to early NK cells. Human Immunology 62, 782-790 (2001). (C) American Soc iety for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.