Sun Wenji, Wang Yi, East James E, Kimball Amy S, Tkaczuk Katherine, Kesmodel Susan, Strome Scott E, Webb Tonya J
Department of Microbiology and Immunology, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States.
Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, PR China.
Cytokine. 2015 Mar;72(1):48-57. doi: 10.1016/j.cyto.2014.12.009. Epub 2015 Jan 5.
Invariant natural killer T (iNKT) cells constitute an important subset of T cells that can both directly and indirectly mediate anti-tumor immunity. However, cancer patients have a reduction in both iNKT cell number and function, and these deficits limit the potential clinical application of iNKT cells for cancer therapy. To overcome the problem of limited iNKT cell numbers, we investigated whether iNKT cells can be generated in vitro from bone marrow-derived adult hematopoietic stem-progenitor cells (HSPC). Our data demonstrate that co-culture of HSPC with OP9-DL1 stromal cells, results in a functional CD3(+) T cell population. These T cells can be further differentiated into iNKT cells by secondary culture with CD1d-Ig-based artificial antigen-presenting cells (aAPC). Importantly, these in vitro-generated iNKT cells are functional, as demonstrated by their ability to proliferate and secrete IFN-γ and GM-CSF following stimulation.
不变自然杀伤T（iNKT）细胞是T细胞的一个重要亚群，能够直接和间接介导抗肿瘤免疫。然而，癌症患者的iNKT细胞数量和功能均有所下降，这些缺陷限制了iNKT细胞在癌症治疗中的潜在临床应用。为了克服iNKT细胞数量有限的问题，我们研究了能否从骨髓来源的成体造血干祖细胞（HSPC）体外生成iNKT细胞。我们的数据表明，HSPC与OP9-DL1基质细胞共培养可产生功能性CD3(+) T细胞群体。通过与基于CD1d-Ig的人工抗原呈递细胞（aAPC）进行二次培养，这些T细胞可进一步分化为iNKT细胞。重要的是，这些体外生成的iNKT细胞具有功能，刺激后它们能够增殖并分泌IFN-γ和GM-CSF，这证明了这一点。
