Cord blood comprises antigen-experienced T cells specific for maternal minor histocompatibility antigen HA-1.
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.
Mommaas
Bregje
B
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Stegehuis-Kamp
Janine A
JA
van Halteren
Astrid G
AG
Kester
Michel
M
Enczmann
Jürgen
J
Wernet
Peter
P
Kögler
Gesine
G
Mutis
Tuna
T
Brand
Anneke
A
Goulmy
Els
E
D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002469:Cell Separation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D005333:Fetus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D015778:Minor Histocompatibility Antigens / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D009842:Oligopeptides / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; C110615:HA-1 antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens; D009842:Oligopeptides