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

JA Gutman, CJ Turtle, TJ Manley… - Blood, The Journal …, 2010 - ashpublications.org
JA Gutman, CJ Turtle, TJ Manley, S Heimfeld, ID Bernstein, SR Riddell, C Delaney
Blood, The Journal of the American Society of Hematology, 2010ashpublications.org
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-γ (IFN-γ) in response to the nonengrafting …
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-γ (IFN-γ) in response to the nonengrafting unit. No significant population of IFN-γ–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-γ–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.
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