Lovastatin inhibits T-cell proliferation while preserving the cytolytic function of EBV, CMV, and MART-1-specific CTLs.
Lovastatin inhibits T-cell proliferation while preserving the cytolytic function of EBV, CMV, and MART-1-specific CTLs.
复制标题
DOI：
10.1097/cji.0b013e3181fb0486
复制
发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Li D;Li Y;Hernandez JA;Patenia R;Kim TK;Khalili J;Dougherty MC;Hanley PJ;Bollard CM;Komanduri KV;Hwu P;Champlin RE;Radvanyi LG;Molldrem JJ;Ma Q
他汀类药物治疗已被证明可以减少移植物抗宿主病（GVHD），同时保留异基因干细胞移植（allo-HCT）中的移植物抗肿瘤（GVT）效应。在此，我们研究了洛伐他汀治疗是否影响人细胞溶解性T淋巴细胞（CTL）的功能。在TCR刺激后，洛伐他汀显著抑制来自健康供体的CD 4+和CD 8 + T细胞的增殖，而其细胞内细胞因子（包括IFN-γ和TNF-α）的产生保持不变，IL-2轻微降低。此外，特异性裂解靶细胞的CTL细胞系来源于患者和正常供体特异性EBV编码的抗原LMP 2或CMV编码的抗原pp 65是不妥协的洛伐他汀的存在下。此外，我们评估了洛伐他汀对来自黑色素瘤患者的MART-1抗原特异性的CD 8+肿瘤浸润淋巴细胞（TIL）的增殖和效应功能的影响。洛伐他汀显著降低了MART-1刺激后抗原特异性TIL的扩增。然而，TIL的效应功能，包括靶细胞的特异性裂解和细胞因子IFN-γ的分泌，在洛伐他汀处理下保持完整。总之，这些数据表明，洛伐他汀抑制EBV-，CMV-和MART-1-特异性CTL的增殖，而不影响细胞溶解能力。洛伐他汀对CTL增殖和细胞毒性的不同影响可能有助于阐明同种免疫反应引起的GVHD和GVT效应的可能机制。
Statin treatment has been shown to reduce graft-versus-host disease (GVHD) while preserving graft-versus-tumor (GVT) effect in allogeneic stem cell transplantation (allo-HCT). Herein, we investigated whether lovastatin treatment affects the function of human cytolytic T lymphocytes (CTLs). Upon TCR stimulation, lovastatin significantly inhibited the proliferation of both CD4+ and CD8+ T cells from healthy donors while their intracellular cytokine production including IFN-γ and TNF-α remained the same with a slight decrease of IL-2. Moreover, the specific lysis of target cells by CTL lines derived from patients and normal donors specific for EBV-encoded antigen LMP2 or CMV-encoded antigen pp65 was uncompromised in the presence of lovastatin. In addition, we evaluated the effect of lovastatin on the proliferation and effector function of the CD8+ tumor–infiltrating lymphocytes (TILs) derived from melanoma patients specific for MART-1 antigen. Lovastatin significantly reduced the expansion of antigen-specific TILs upon MART-1 stimulation. However, the effector function of TILs, including the specific lysis of target cells and secretion of cytokine IFN-γ, remained intact with lovastatin treatment. Taken together, these data demonstrated that lovastatin inhibits the proliferation of EBV-, CMV- and MART-1-specific CTLs without affecting cytolytic capacity. The differential effect of lovastatin on the proliferation versus cytoxicity of CTLs might shed some light on elucidating the possible mechanisms of GVHD and GVT effect elicited by alloimmune responses.