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Cord blood comprises antigen-experienced T cells specific for maternal minor histocompatibility antigen HA-1

2004; Elsevier BV; Volume: 105; Issue: 4 Linguagem: Inglês

10.1182/blood-2004-07-2832

1528-0020

Bregje Mommaas, Janine A. Stegehuis-Kamp, Astrid G. S. van Halteren, Michel D.G. Kester, Jürgen Enczmann, Peter Wernet, Gesine Kögler, Tuna Mutis, Anneke Brand, Els Goulmy,

Prenatal Screening and Diagnostics

Abstract 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 feasibility of ex vivo generation of minor H antigen HA-1-specific T cells from cord blood cells. Moreover, we observed pre-existing HA-1-specific T cells in cord blood samples. Both the circulating and the ex vivo-generated HA-1-specific T cells show specific and hematopoietic restricted lysis of human leukocyte antigen-A2pos/HA-1pos (HLA-A2pos/HA-1pos) target cells, including leukemic cells. The cord blood-derived HA-1-specific cytotoxic T cells are from child origin. Thus, the so-called naive cord blood can comprise cytotoxic T cells directed at the maternal minor H antigen HA-1. The apparent immunization status of cord blood may well contribute to the in vivo graft-versus-leukemia activity after transplantation. Moreover, since the fetus cannot be primed against Y chromosome-encoded minor H antigens, cord blood is an attractive stem cell source for male patients. (Blood. 2005;105:1823-1827)