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

• Published in: Blood 2005-02, Vol.105 (4), p.1823-1827
• Main Authors: Mommaas, Bregje, Stegehuis-Kamp, Janine A., van Halteren, Astrid G., Kester, Michel, Enczmann, Jürgen, Wernet, Peter, Kögler, Gesine, Mutis, Tuna, Brand, Anneke, Goulmy, Els
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Differentiation - immunology; Cell Line; Cell Line, Tumor; Cell Separation; Cells, Cultured; Cytotoxicity, Immunologic; Epitopes, T-Lymphocyte - immunology; Female; Fetal Blood - cytology; Fetal Blood - immunology; Fetal Blood - metabolism; Fetus - cytology; Fetus - immunology; Fetus - metabolism; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; HLA-A2 Antigen - biosynthesis; Humans; Maternal-Fetal Exchange - immunology; Medical sciences; Minor Histocompatibility Antigens - biosynthesis; Minor Histocompatibility Antigens - blood; Minor Histocompatibility Antigens - immunology; Oligopeptides - biosynthesis; Oligopeptides - blood; Oligopeptides - immunology; Pregnancy; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Cytotoxic - cytology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-07-2832

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)