Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit.
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.
Gutman
Jonathan A
JA
Division of Medical Oncology, 1665 Aurora Ct, Room 2251A, Aurora, CO 80045, USA. jgutman@fhcrc.org
Turtle
Cameron J
CJ
Manley
Thomas J
TJ
Heimfeld
Shelly
S
Bernstein
Irwin D
ID
Riddell
Stanley R
SR
Delaney
Colleen
C
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
D007371:Interferon-gamma