Generation of functional, antigen-specific CD8+ human T cells from cord blood stem cells using exogenous Notch and tetramer-TCR signaling.
Generation of functional, antigen-specific CD8+ human T cells from cord blood stem cells using exogenous Notch and tetramer-TCR signaling.
复制标题
DOI：
10.1002/stem.1512
复制
发表时间：
2014-01
期刊：
影响因子：
5.2
通讯作者：
Roy, Krishnendu
中科院分区：
文献类型：
--
作者：
Fernandez, Irina;Ooi, Tracy P.;Roy, Krishnendu
In vitro differentiation of mouse and human stem cells into early T cells has been successfully demonstrated using artificial Notch signaling systems. However, generation of mature, antigen-specific, functional T cells, directly from human stem cells has remained elusive, except when using stromal co-culture of stem cells retrovirally transfected with antigen-specific T cell receptors (TCRs). Here we show that human umbilical cord blood (UCB)-derived CD34+CD38−/low hematopoietic stem cells (HSCs) can be successfully differentiated into functional, antigen-specific cytotoxic CD8+ T cells without direct stromal co-culture or retroviral TCR transfection. Surface-immobilized Notch ligands (DLL1) and stromal cell conditioned medium successfully induced the development of CD1a+CD7+ and CD4+CD8+ early T cells. These cells, upon continued culture with cytomegalovirus (CMV) or Influenza-A virus epitope-loaded HLA-A*0201 tetramers, resulted in the generation of a polyclonal population of CMV-specific or Influenza-specific CD8+ T cells respectively. Upon further activation with antigen-loaded target cells, these antigen-specific, stem cell-derived T cells exhibited cytolytic functionality, specifically CD107a surface mobilization, IFNγ production, and Granzyme B secretion. Such scalable, in vitro generation of functional, antigen-specific human T cells from human stem cells could eventually provide a readily available cell source for adoptive transfer immunotherapies and also allow better understanding of human T cell development.
登录
查看更多内容
影响因子：
6.4
作者：
Lacey, SF;Martinez, J;Diamond, DJ
通讯作者：
Diamond, DJ
影响因子：
3.9
作者：
Dudley, ME;Wunderlich, J;Rosenberg, SA
通讯作者：
Rosenberg, SA
影响因子：
4.4
作者：
Dervovic, Dzana D.;Ciofani, Maria;Zuniga-Pfluecker, Juan Carlos
通讯作者：
Zuniga-Pfluecker, Juan Carlos
白介素7受体伽马基因重排的受体控制：受体相关链和位点可及性的作用。
DOI：
10.1084/jem.188.12.2233
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Durum SK;Candèias S;Nakajima H;Leonard WJ;Baird AM;Berg LJ;Muegge K
通讯作者：
Muegge K
Notch配体delta1的密度决定了造血干细胞的B和T细胞前体的产生。
影响因子：
15.3
作者：
Dallas, MH;Varnum- Finney, B;Delaney, C;Kato, K;Bernstein, ID
通讯作者：
Bernstein, ID