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

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-A2(pos)/HA-1(pos) (HLA-A2(pos)/HA-1(pos)) 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.

• Authors: Bregje Mommaas, Janine A Stegehuis-Kamp, Astrid G van Halteren, Michel Kester, Jürgen Enczmann, Peter Wernet, Gesine Kögler, Tuna Mutis, Anneke Brand, Els Goulmy
• Journal: Blood (Blood) Vol. 105 Issue 4 Pg. 1823-7 (Feb 15 2005) ISSN: 0006-4971 [Print] United States
• PMID: 15498856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• HA-1 antigen
• HLA-A2 Antigen
• Minor Histocompatibility Antigens
• Oligopeptides

Topics

• Cell Differentiation (immunology)
• Cell Line
• Cell Line, Tumor
• Cell Separation
• Cells, Cultured
• Cytotoxicity, Immunologic
• Epitopes, T-Lymphocyte (immunology)
• Female
• Fetal Blood (cytology, immunology, metabolism)
• Fetus (cytology, immunology, metabolism)
• HLA-A2 Antigen (biosynthesis)
• Hematopoietic Stem Cells (cytology, immunology)
• Humans
• Maternal-Fetal Exchange (immunology)
• Minor Histocompatibility Antigens (biosynthesis, blood, immunology)
• Oligopeptides (biosynthesis, blood, immunology)
• Pregnancy
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes, Cytotoxic (cytology, immunology, metabolism)