霉酚酸和静脉注射免疫球蛋白对混合淋巴细胞反应中的细胞增殖和凋亡有相加作用。
Mycophenolic acid and intravenous immunoglobulin exert an additive effect on cell proliferation and apoptosis in the mixed lymphocyte reaction.
机构信息
Transplant Immunology Laboratory, Comprehensive Transplant Center, Cedars-Sinai Medical Center/UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
出版信息
Transpl Immunol. 2010 Jul;23(3):117-20. doi: 10.1016/j.trim.2010.04.009. Epub 2010 May 5.
BACKGROUND
Intravenous immunoglobulin (IVIG) has known immunomodulatory effects in autoimmune diseases and transplantation and is commonly used in desensitization protocols and for treatment of antibody-mediated rejection (AMR). IVIG inhibits the MLR and induces apoptosis in immune cells. Mycophenolate mofetil inhibits immune cell proliferation and is an effective immunsuppressive agent. Here, we examined the possible synergistic effects of combined MMF and IVIG on cell proliferation and apoptosis induction in the MLR.
METHODS
Two-way MLRs were performed with mycophenolic acid (MPA), IVIG and both in combination. Cell proliferation and apoptosis were detected by 3H-thymidine incorporation and Annexin flow cytometry, respectively.
RESULTS
IVIG (1-10mg/ml) or MPA (0.01-0.25 microg/ml) alone inhibited cell proliferation in the MLR in a dose-dependent manner. MPA at 0.01-0.03 microg/ml showed minimal inhibition, but the addition of 5 and 10mg/ml IVIG increased inhibition significantly (p<0.05) to 43% and 64%, respectively. Annexin V positive cell number was significantly higher in IVIG (5mg/ml) treated CD19+ cells (68+/-13% vs. 43+/-12%, p=0.001) compared to untreated cells and to a lesser degree in CD3+ cells (29+/-7% vs. 25+/-10 %, p=0.02). MPA (0.25-10 microg/ml) alone neither induced nor inhibited apoptosis. Addition of MPA had no effect on apoptosis induced by IVIG.
CONCLUSION
- Combining low concentrations of IVIG (5-10 mg/ml) and MPA (0.01-0.03 microg/ml)has an additive effect on inhibition of cell proliferation in the MLR. 2) MPA alone neither induces nor inhibits apoptosis in T or B cells in the MLR, and has no effect on apoptosis induced by IVIG. These in vitro observations may have implications for modification of therapeutic approaches to protocols utilizing IVIG for desensitization and immune modulation.
背景
静脉注射免疫球蛋白（IVIG）在自身免疫性疾病和移植中具有已知的免疫调节作用，常用于脱敏方案和治疗抗体介导的排斥反应（AMR）。IVIG 抑制 MLR 并诱导免疫细胞凋亡。霉酚酸酯（MMF）抑制免疫细胞增殖，是一种有效的免疫抑制剂。在这里，我们研究了 MMF 和 IVIG 联合使用对 MLR 中细胞增殖和凋亡诱导的可能协同作用。
方法
用霉酚酸（MPA）、IVIG 及两者联合进行双向 MLR。通过 3H-胸腺嘧啶掺入和 Annexin 流式细胞术分别检测细胞增殖和凋亡。
结果
IVIG（1-10mg/ml）或 MPA（0.01-0.25μg/ml）单独以剂量依赖性方式抑制 MLR 中的细胞增殖。MPA 浓度为 0.01-0.03μg/ml 时抑制作用最小，但加入 5 和 10mg/ml IVIG 可显著增加抑制作用（p<0.05），分别达到 43%和 64%。与未经处理的细胞相比，用 5mg/ml IVIG 处理的 CD19+细胞中 Annexin V 阳性细胞数显著增加（68+/-13%对 43+/-12%，p=0.001），而 CD3+细胞中 Annexin V 阳性细胞数增加程度较小（29+/-7%对 25+/-10%，p=0.02）。MPA（0.25-10μg/ml）单独既不诱导也不抑制凋亡。MPA 对 IVIG 诱导的凋亡无影响。
结论
1）联合使用低浓度 IVIG（5-10mg/ml）和 MPA（0.01-0.03μg/ml）对 MLR 中细胞增殖的抑制具有相加作用。2）MPA 单独在 MLR 中既不诱导也不抑制 T 或 B 细胞凋亡，也不影响 IVIG 诱导的凋亡。这些体外观察结果可能对修改利用 IVIG 进行脱敏和免疫调节的方案中的治疗方法具有重要意义。
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