Ex vivo expansion and Th1/Tc1 maturation of umbilical cord blood T cells by CD3/CD28 costimulation.
Ex vivo expansion and Th1/Tc1 maturation of umbilical cord blood T cells by CD3/CD28 costimulation.
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DOI：
10.1016/j.bbmt.2008.07.016
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发表时间：
2008-10
影响因子：
4.3
通讯作者：
Szabolcs, Paul
中科院分区：
文献类型：
--
作者：
Mazur, Melissa A.;Davis, Craig C.;Szabolcs, Paul
One of the major limitations of unrelated umbilical cord blood transplantation (UCBT) is the lack of donor cells available for post-transplant donor leukocyte infusions (DLI) to boost immunity or induce GVL. Starting from ~5% fraction of a UCB graft we report the feasibility and biological characteristics of ex vivo expansion of frozen/thawed cord blood T cells by anti-CD3 and anti-CD28 antibody-coated Dynal beads in the presence of IL-2. We postulated that while undergoing expansion, CB T cells may mature towards a Th1/Tc1 phenotype and acquire the potential for cytotoxicity. While an almost 2 log expansion also led to the acquisition of IL-12Rα and increase in Th1 characteristics, post-expansion lymphocytes produced less IFNγ, TNFα, Granzyme B, stored almost no perforin, and lacked cytotoxicity against allogeneic targets. Collectively, these suggest relative safety from acute/hyperacute GVHD. CD8+ T cells expanded preferentially while a higher rate of apoptosis among CD4+ T cells promoted an inverted CD4/CD8 ratio. Most expanded T cells retained expression of CD27, CD28, L-selectin, however, the majority down regulated CCR-7. In sum, CB T cell proliferation sustained by CD3/CD28 costimulatory 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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