Umbilical cord blood transplantation is applied as treatment for mainly pediatric patients with hematologic malignancies. The clinical results show a relatively low incidence of graft-versus-host disease and leukemia relapse. Since maternal cells traffic into the fetus during pregnancy, we questioned whether cord blood has the potential to generate cytotoxic T cells specific for the hematopoietic minor histocompatibility (H) antigen HA-1 that would support the graft-versus-leukemia effect. Here, we demonstrate the feasibil- IntroductionIn the last decade, umbilical cord blood transplantation (CBT) has been available as an alternative to human leukocyte antigen (HLA)-matched sibling or unrelated donor stem cell transplantation (SCT) for the treatment of hematologic malignancies. [1][2][3][4][5][6][7] The clinical outcome of transplanted CB grafts with 1 or 2 HLA antigen mismatches demonstrates a similar risk of developing graft-versushost disease (GvHD) as compared to HLA-matched unrelated SCT. 5,6 A significant lower incidence of acute and chronic GvHD was reported after HLA-identical CBT when compared to sibling SCT. 4 Collectively, these clinical results point to a decreased incidence of GvHD after CBT.GvHD is often associated with a curative graft-versus-leukemia (GvL) response. Minor H antigen disparities between donor and recipient play important roles in both the GvH and GvL reactivity after HLA-matched SCT as reviewed. 8 One of the well-described minor H antigens is HA-1. The immunodominant minor H antigen HA-1 is encoded by a diallelic gene with a single amino acid polymorphism. 9 The HA-1 "positive" allele (HA-1 pos ) contains a histidine at position 3 (HA-1 H ), whereas the HA-1 "negative" allele (HA-1 neg ) contains an arginine (HA-1 R ). The HA-1 H peptide is recognized by HLA-A2-restricted CD8 pos cytotoxic T cells from HA-1 neg donors. [10][11][12] The expression of HA-1 is restricted to the hematopoietic lineage and to epithelial carcinomas. 13,14 This restricted expression makes HA-1 an attractive target antigen for GvL and graft-versus-tumor responses. 15 Despite the lower incidence of GvHD after CBT, there is no indication of increased leukemia relapse rates when compared with sibling or unrelated donor SCT. [3][4][5] Comparable survival rates point to an as-yet-unexplored GvL potential of cord blood. Relatively little is known about the development of antigenspecific T-cell responses around birth. 16 Mature monocytederived neonatal dendritic cells (DCs) are able to efficiently prime antigen-specific cytotoxic T cells in vitro. 17 In bulk cultures, cord blood T cells proliferate in response to alloantigen. 18 Yet the development of functional alloreactive cytotoxic T cells is impaired. [18][19][20] Limiting dilution studies have, however, reported normal precursor frequencies of cytotoxic T cells specific for allo-HLA class I and class II in cord blood. [20][21][22] Thus, the capacity to develop allogeneic cytotoxic T cells is intact at birth, despite overall diminished magnitude of responses....
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