Tesar B M, Du W, Shirali A C, Walker W E, Shen H, Goldstein D R
Department of Internal Medicine, Yale University School of Medicine, Yale University, New Haven, CT, USA.
Am J Transplant. 2009 Jan;9(1):54-63. doi: 10.1111/j.1600-6143.2008.02458.x. Epub 2008 Oct 31.
As increasing numbers of elderly patients require solid organ transplantation, the need to better understand how aging modifies alloimmune responses increases. Here, we examined whether aged mice exhibit augmented, donor-specific memory responses prior to transplantation. We found that elevated donor-specific IL-17, but not IFN-gamma, responses were observed in aged mice compared to young mice prior to transplantation. Further characterization of the heightened IL-17 alloimmune response with aging demonstrated that memory CD4(+) T cells were required. Reduced IL-2 alloimmune responses with age contributed to the elevated IL-17 phenotype in vitro, and treatment with an anti-IL-17 antibody delayed the onset of acute allograft rejection. In conclusion, aging leads to augmented, donor-specific IL-17 immune responses that are important for the timing of acute allograft rejection in aged recipients. IL-17 targeting therapies may be useful for averting transplant rejection responses in older transplant recipients.
随着越来越多的老年患者需要实体器官移植，更好地了解衰老如何改变同种免疫反应的需求也在增加。在这里，我们研究了老年小鼠在移植前是否表现出增强的供体特异性记忆反应。我们发现，与年轻小鼠相比，老年小鼠在移植前观察到供体特异性白细胞介素-17（IL-17）反应升高，但干扰素-γ（IFN-γ）反应未升高。对衰老过程中增强的IL-17同种免疫反应的进一步表征表明，记忆性CD4(+) T细胞是必需的。随着年龄增长，IL-2同种免疫反应降低在体外导致了IL-17表型升高，用抗IL-17抗体治疗可延迟急性移植排斥反应的发生。总之，衰老导致增强的供体特异性IL-17免疫反应，这对老年受者急性移植排斥反应的发生时间很重要。靶向IL-17的疗法可能有助于避免老年移植受者的移植排斥反应。
