title: Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit.
abstract: We investigated the potential role of an immune reaction in mediating the dominant engraftment of 1 cord blood unit in 14 patients who received a double-unit cord blood transplantation (CBT). In 10 patients, dominant engraftment of a single donor unit emerged by day 28 after CBT. In 9 of these 10 patients, a significant subset of CD8(+) CD45RO(+/-)CCR7(-) T cells, present in peripheral blood mononuclear cells and derived from the engrafting cord blood unit, produced interferon-gamma (IFN-gamma) in response to the nonengrafting unit. No significant population of IFN-gamma-secreting cells was detectable when posttransplantation peripheral blood mononuclear cells were stimulated against cells from the engrafted unit (P < .001) or from a random human leukocyte antigen disparate third party (P = .003). Three patients maintained persistent mixed chimerism after CBT, and no significant IFN-gamma-secreting cells were detected after similar stimulations in these patients (P < .005). Our data provide the first direct evidence in human double-unit CBT recipients that immune rejection mediated by effector CD8(+) T cells developing after CBT from naive precursors is responsible for the failure of 1 unit to engraft. Future investigations based on these findings may result in strategies to predict a dominant unit and enhance graft-versus-leukemia effect.
authors.affiliation: Division of Medical Oncology, 1665 Aurora Ct, Room 2251A, Aurora, CO 80045, USA. jgutman@fhcrc.org
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Gutman
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Turtle
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Manley
authors.forename: Shelly
authors.initials: S
authors.lastname: Heimfeld
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Bernstein
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.forename: Colleen
authors.initials: C
authors.lastname: Delaney
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning; D055815:Young Adult
chemical_list: D007371:Interferon-gamma