Journal
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 14, Issue 10, Pages 1190-1196Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2008.07.016
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Funding
- National Institutes of Health [IP01-HL-67314-01A1, 1R01CA132110-1]
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One major limitation of UCBT is the lack of donor cells available for posttransplantation donor leukocyte infusions (DLI) to boost immunity or induce graft-versus-leukemia (GVL) activity. Starting from a similar to 5% fraction of a UCB graft, we report the feasibility and biological characteristics of ex vivo expansion of frozen/thawed CB T cells by anti-CID3 and anti-CD28 antibody-coated Dynal beads in the presence of interleukin (IL)-2. We postulated that while undergoing expansion, UCB T cells may mature toward a ThI/TcI phenotype and acquire the potential for cytotoxicity. Whereas an almost 2-log expansion also led to the acquisition of IL-I2R alpha and an increase in ThI characteristics, postexpansion lymphocytes produced less nterferon-gamma, tumor necrosis factor-a, and granzyme B; stored almost no perforin; and lacked cytotoxicity against allogeneic targets. Collectively, these suggest relative safety from acute/hyperacute graft-versus-host disease. CD8(+) T cells expanded preferentially, whereas a higher rate of apoptosis in CD4(+) T cells also promoted an inverted CD4/CD8 ratio. Most expanded T cells retained expression of CD27, CD28, and L-selectin but down-regulated CCR-7. In summary, UCB T cell proliferation sustained by CD3/CD28 co-stimulatory beads and IL-2 can lead to clinically relevant doses of DLI from a very small fraction of the UCB graft, although future strategies to reduce apoptosis may enhance their clinical potential.
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