In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes

In vitro priming and expansion of cytomegalovirus-specific Th1 and Tc1 T cells from naive cord blood lymphocytes
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DOI:
10.1182/blood-2005-10-006536
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发表时间:
2006-09-01
期刊:
影响因子:
20.3
通讯作者:
Szabolcs, Paul
Szabolcs, Paul
中科院分区:
医学1区
文献类型:
--
作者:
Park, Kyung-Duk;Marti, Luciana;Szabolcs, Paul

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Adoptive transfer of CMV-specific cytotoxic T cells (CTLs) expanded in vitro from memory donor T cells can reduce the incidence of CMV disease in allogeneic transplant recipients. However, this approach has been unavailable in the cord blood (CB) transplantation setting because CB T cells are antigen naive and biased toward Th2/Tc2 function. We developed a protocol to in vitro prime and expand CMV-specific CTLs from CB. T cells were primed with cytokines to trigger skewing toward Th1/Tc1 lineage before encountering monocyte and CD34(+) progenitor-derived dendritic cells loaded with CMV antigen and its immune complex. CMV-pulsed cultures expanded significantly more over 4 to 6 weeks than CMV cultures despite identical cytokine milieu. T cells isolated from CMV+ cultures showed a preferential expansion of CD45RA(-)/RO+/CD27(+) T cells compared to CMV- cultures. CMV-specific IFN-gamma and TNF-alpha-producing CD4(+) (Th1) and CD8(+) (Tc1) T cells were enriched after 3 to 4 weeks and CMV-specific cytotoxicity developed 1 to 2 weeks later.