Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit.

Publication Type:

Journal Article

Source:

Blood, Volume 115, Issue 4, p.757-65 (2010)

Keywords:

2010, Adolescent, Adult, Aged, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Processing Core Facility, Center-Authored Paper, Clinical Research Division, Cord Blood Stem Cell Transplantation, Flow Cytometry Core Facility, Graft Rejection, Graft vs Leukemia Effect, Hematopoiesis, Hematopoietic Stem Cells, Humans, interferon-gamma, LEUKEMIA, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Acute, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Shared Resources, Transplantation Chimera, Transplantation Conditioning, Young Adult

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.