title: CD4+ T-cell alloreactivity toward mismatched HLA class II alleles early after double umbilical cord blood transplantation.
abstract: Although double umbilical cord blood transplantation (dUCBT) in adult patients may be associated with less graft failure compared with single UCBT, hematopoietic recovery generally originates from a single cord blood unit (CBU). CBU predominance is still incompletely understood. We recently showed that blood CD4+T-cell numbers rapidly increase after dUCBT, and early CD4+T-cell chimerism predicts for graft predominance. Given the frequent HLA class II allele mismatches between CBUs in dUCBT, we hypothesized that alloreactive HLA class II-specific CD4+T cells from the "winning" CBU may contribute to rejection of the "loser" CBU. We evaluated whether CD4+T cells originating from the predominant (PD)-CBU would recognize HLA class II allele mismatches, expressed by the nonengrafting (NE)-CBU. Alloreactive effector CD4+T cells toward 1 or more mismatched HLA class II alleles of the NE-CBU were detected in 11 of 11 patients, with reactivity toward 29 of 33 (88%) tested mismatches, and the strongest reactivity toward DR and DQ alleles early after dUCBT. Mismatched HLA class II allele-specific CD4+T cells recognized primary leukemic cells when the mismatched HLA class II allele was shared between NE-CBU and patient. Our results suggest that cytotoxicity exerted by CD4+T cells from the PD-CBU drives the rapid rejection of the NE-CBU, whose alloreactive effect might also contribute to graft-versus-leukemia.
authors.affiliation: Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Cor H J
authors.identifier: 0000-0002-6887-1377
authors.initials: CH
authors.lastname: Lamers
authors.affiliation: Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wijers
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis A M
authors.identifier: 0000-0001-6386-4517
authors.initials: CA
authors.lastname: van Bergen
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; and Department of Transfusion Medicine, Sanquin Blood Supply, Rotterdam, The Netherlands.
authors.forename: Judith A E
authors.initials: JA
authors.lastname: Somers
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; and.
authors.forename: Eric
authors.initials: E
authors.lastname: Braakman
authors.affiliation: Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Gratama
authors.affiliation: Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Reno
authors.identifier: 0000-0002-3649-807X
authors.initials: R
authors.lastname: Debets
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J H Frederik
authors.identifier: 0000-0002-9819-4813
authors.initials: JH
authors.lastname: Falkenburg
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; and.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000328:Adult; D000483:Alleles; D064591:Allografts / Q000276:immunology*; D000741:Anemia, Aplastic / Q000628:therapy; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D046528:Chimerism; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008875:Middle Aged
chemical_list: D000949:Histocompatibility Antigens Class II