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, Els Goulmy*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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-AS pos/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.

Original languageEnglish
Pages (from-to)1823-1827
Number of pages5
JournalBlood
Volume105
Issue number4
DOIs
Publication statusPublished - 15 Feb 2005
Externally publishedYes

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