Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, West Bengal 700026, India.
Vaccine. 2010 Feb 3;28(5):1241-52. doi: 10.1016/j.vaccine.2009.11.018. Epub 2009 Dec 5.
In an objective to find out an effective, nontoxic dendritic cell (DC) maturating agent for human use, CD14(+) monocytes were differentiated with GMCSF/IL-4 and matured with neem leaf glycoprotein (NLGP). NLGP matured DCs (NLGP-DCs) show upregulated expression of CD83, CD80, CD86, CD40 and MHCs, in a comparable extent of control, LPS. NLGP-DCs secrete high amount of IL-12p70 with low IL-10. NLGP upregulates the expression of crucial transcription factor, ikaros, indicating maturation towards DC1 phenotype. Increased expression of CD28 and CD40L on T cells following co-culture with NLGP-DCs was noticed to promote DC-T interactions. As a result, T cells secrete high amount of IFN gamma with low IL-4 and generates anti-tumor type 1 immune microenvironment. Such NLGP-DCs present carcinoembryonic antigen (CEA) effectively to T cells to increase T cell mediated cytotoxicity of CEA(+) tumor cells in vitro and in vivo. With emergence of the NLGP as a promising DC maturating agent, NLGP-DCs can be used as a candidate vaccine tool for antigen specific cancer immunotherapy.
为了寻找一种有效的、无毒的树突状细胞（DC）成熟剂用于人体，我们使用 GMCSF/IL-4 将 CD14(+)单核细胞分化为树突状细胞，并用印楝叶糖蛋白（NLGP）使其成熟。NLGP 成熟的树突状细胞（NLGP-DCs）表现出上调的 CD83、CD80、CD86、CD40 和 MHCs 的表达，与对照 LPS 相当。NLGP-DCs 分泌大量的 IL-12p70，同时产生少量的 IL-10。NLGP 上调了关键转录因子 ikaros 的表达，表明其向 DC1 表型成熟。与 NLGP-DCs 共培养后，T 细胞上 CD28 和 CD40L 的表达增加，促进了 DC-T 相互作用。结果，T 细胞分泌大量 IFNγ，同时产生少量的 IL-4，从而产生抗肿瘤的 1 型免疫微环境。这种 NLGP-DCs 能够有效地向 T 细胞呈递癌胚抗原（CEA），从而增加 T 细胞对体外和体内 CEA(+)肿瘤细胞的细胞毒性。随着 NLGP 作为一种有前途的 DC 成熟剂的出现，NLGP-DCs 可作为抗原特异性癌症免疫治疗的候选疫苗工具。
