人工抗原呈递细胞联合 IL-15 和 IL-21 可有效诱导黑色素瘤特异性细胞毒性 CD8+ CD28+ T 淋巴细胞反应。
Artificial antigen-presenting cells plus IL-15 and IL-21 efficiently induce melanoma-specific cytotoxic CD8+ CD28+ T lymphocyte responses.
机构信息
Biological Targeting Diagonosis and Therapy Research Center, Guangxi Medical University, Nanning, Guangxi 530021, PR China.
出版信息
Asian Pac J Trop Med. 2013 Jun;6(6):467-72. doi: 10.1016/S1995-7645(13)60076-0.
OBJECTIVE
To develop a novel artificial antigen-presenting system for efficiently inducing melanoma-specific CD8(+) CD28(+) cytotoxic T lymphocyte (CTL) responses.
METHODS
Cell-sized Dynabeads® M-450 Epoxy beads coated with H-2K(b): Ig-TRP2180-188 and anti-CD28 antibody were used as artificial antigen-presenting cells (aAPCs) to induce melanoma-specific CD8(+)CD28(+) CTL responses with the help of IL-21 and IL-15. Dimer staining, proliferation, ELISPOT, and cytotoxicity experiments were conducted to evaluate the frequency and activity of induced CTLs.
RESULTS
Dimer staining demonstrated that the new artificial antigen-presenting system efficiently induced melanoma TRP2-specific CD8(+)CD28(+)CTLs. Proliferation and ELISPOT assays indicated that the induced CTLs rapidly proliferate and produce increased IFN- γ under the stimulation of H-2K(b): Ig-TRP2-aAPCs, IL-15, and IL-21. In addition, cytotoxicity experiments showed that induced CTLs have specific killing activity of target cells.
CONCLUSIONS
The new artificial antigen-presenting system including aAPCs plus IL-21 and IL-15 can induce a large number of antigen-specific CD8(+) CD28(+) CTLs against the melanoma. Our study provides evidence for a novel adoptive immunotherapy against tumors.
目的
开发一种新型人工抗原呈递系统，以有效诱导黑色素瘤特异性 CD8(+)CD28(+)细胞毒性 T 淋巴细胞（CTL）反应。
方法
用 H-2K(b): Ig-TRP2180-188 和抗 CD28 抗体包被的细胞大小的 Dynabeads® M-450 Epoxy 珠作为人工抗原呈递细胞（aAPC），在 IL-21 和 IL-15 的帮助下诱导黑色素瘤特异性 CD8(+)CD28(+)CTL 反应。进行二聚体染色、增殖、ELISPOT 和细胞毒性实验，以评估诱导的 CTL 的频率和活性。
结果
二聚体染色表明，新型人工抗原呈递系统能够有效诱导黑色素瘤 TRP2 特异性 CD8(+)CD28(+)CTL。增殖和 ELISPOT 实验表明，在 H-2K(b): Ig-TRP2-aAPC、IL-15 和 IL-21 的刺激下，诱导的 CTL 迅速增殖并产生更多的 IFN-γ。此外，细胞毒性实验表明诱导的 CTL 对靶细胞具有特异性杀伤活性。
结论
新型人工抗原呈递系统包括 aAPC 加 IL-21 和 IL-15，可诱导大量针对黑色素瘤的抗原特异性 CD8(+)CD28(+)CTL。我们的研究为肿瘤的新型过继免疫治疗提供了证据。
Zotero 插件