1. Single-unit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit
by Jonathan A. Gutman, Cameron J. Turtle, Thomas J. Manley, Shelly Heimfeld, Irwin D. Bernstein, Stanley R. Riddell, and Colleen Delaney
Blood
Volume 115(4):
January 28, 2010
©2010 by American Society of Hematology

2. Conversion from naive to effector/effector memory T-cell phenotype after double-cord CBT. (A) CD8+ and CD4+ T cells in a representative unmanipulated fresh cord blood express a naive phenotype (CCR7+CD45RO−).
Conversion from naive to effector/effector memory T-cell phenotype after double-cord CBT. (A) CD8+ and CD4+ T cells in a representative unmanipulated fresh cord blood express a naive phenotype (CCR7+CD45RO−). (B) In a representative sample of day 14 posttransplantation PBMCs, CD8+ T cells express a primarily effector/effector memory phenotype (CCR7−CD45RO+/−), and CD4+ T cells express primarily naive (CCR7+CD45RO−) and central memory (CCR7+CD45RO+) phenotypes.
Jonathan A. Gutman et al. Blood 2010;115:
©2010 by American Society of Hematology

3. Development of IFN-γ–secreting CD8+ T cells recognizing alloantigens expressed by the nonengrafting unit after double-unit CBT. (A) After a 5-hour stimulation, CD8+CD45RO+/−CCR7− IFN-γ–staining cells from PBMCs samples collected 14 to 28 days after transpla...
Development of IFN-γ–secreting CD8+ T cells recognizing alloantigens expressed by the nonengrafting unit after double-unit CBT. (A) After a 5-hour stimulation, CD8+CD45RO+/−CCR7− IFN-γ–staining cells from PBMCs samples collected 14 to 28 days after transplantation are demonstrable against LCLs generated from the nonengrafting unit (i), but not the dominant unit (ii) or a random third party unit (iii). (B) IFN-γ–secreting CD8+ T cells are detectable among 9 of 10 patients establishing single donor dominance. (C) Alloreactive IFN-γ–secreting CD8+ T cells decline at later times after CBT. ■ represents time point at which the sample was drawn; solid lines, no administration of steroids for GVHD in the interval between sample assays; dotted lines, administration of steroids for GVHD in the interval between sample assays. Because 3 patients died before second PBMCs samples were collected, serial data for only 6 patients are shown.
Jonathan A. Gutman et al. Blood 2010;115:
©2010 by American Society of Hematology

4. Host CD8+ T cells reactive with cord blood alloantigens are present in 9 patients rejecting double CBT. Day 26 posttransplantation PBMCs were stimulated against LCLs generated from the transplanted cord units.
Host CD8+ T cells reactive with cord blood alloantigens are present in 9 patients rejecting double CBT. Day 26 posttransplantation PBMCs were stimulated against LCLs generated from the transplanted cord units. (A) The majority of CD3+ cells are CD8+. (B) The CD8+ cells express primarily effector/effector memory phenotype (CD45RO+/−CCR7−). (C) Host CD8+CD45RO+/−CCR7− cells stain positive for intracellular IFN-γ staining after stimulation with each of the transplanted cord unit.
Jonathan A. Gutman et al. Blood 2010;115:
©2010 by American Society of Hematology