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 Blood, 15 February 2005, Vol. 105, No. 4, pp. 1823-1827.
Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2004-07-2832.

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TRANSPLANTATION

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

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

From the Department of Immunohematology and Blood Transfusion; the Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands; the Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich Heine University, Dusseldorf, Germany; and the Sanquin Blood Bank, Leiden, The Netherlands.

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)


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