Lin Syh-Jae, Cheng Po-Jen, Yan Dah-Chin, Lee Pei-Tzu, Hsaio Hsiu-Shan
Division of Allergy and Immunology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chang Gung Children's Hospital, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan.
Transpl Immunol. 2006 Aug;16(2):112-6. doi: 10.1016/j.trim.2006.04.002. Epub 2006 May 30.
Interleukin(IL)-15 is a promising immunotherapeutic agent for immune reconstitution following stem cell transplantation. To investigate whether IL-15 would aggravate graft-versus-host disease (GVHD) in the setting of unrelated umbilical cord blood (CB) transplantation, we examined the effect of IL-15 on activation marker expression, proliferation and cytokine production of CB in a one-way mixed lymphocyte culture (MLC) assay. We found that IL-15 differentially enhanced CD69 and CD25 expression on CB T cells following allo-stimulation. The maximum degree of allo-specific CB proliferation was achieved on Day 6. IL-15 down-regulated the CB alloreactive proliferative response on Days 4, 6, and 8, with preferentially enhanced autologous proliferation. Exogenous IL-15 further enhanced CB TNF-alpha and IL-10 production in both autologous and allogeneic MLC 6 days after allopriming. Thus, IL-15 was effective in enhancing activation marker expression and cytokine production during CB alloreactivity, but failed to enhance allospecific proliferation. Further studies would be needed to study the role of IL-15 on GVHD in the setting of CB transplantation.
白细胞介素(IL)-15是一种在干细胞移植后免疫重建方面颇具前景的免疫治疗药物。为了研究在非亲缘脐血(CB)移植情况下IL-15是否会加重移植物抗宿主病(GVHD),我们在单向混合淋巴细胞培养(MLC)试验中检测了IL-15对CB的活化标志物表达、增殖及细胞因子产生的影响。我们发现,同种异体刺激后,IL-15可差异性增强CB T细胞上CD69和CD25的表达。同种异体特异性CB增殖的最大程度在第6天达到。IL-15在第4、6和8天下调了CB的同种异体反应性增殖反应,同时优先增强了自体增殖。在同种异体初次刺激6天后,外源性IL-15在自体和同种异体MLC中均进一步增强了CB肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)的产生。因此,IL-15在增强CB同种异体反应性期间的活化标志物表达和细胞因子产生方面有效,但未能增强同种异体特异性增殖。需要进一步研究以探讨IL-15在CB移植情况下对GVHD的作用。