Schaenman J M, Rossetti M, Sidwell T, Groysberg V, Sunga G, Korin Y, Liang E, Zhou X, Abdalla B, Lum E, Bunnapradist S, Pham T, Danovitch G, Reed E F
Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
Hum Immunol. 2018 Sep;79(9):659-667. doi: 10.1016/j.humimm.2018.06.006. Epub 2018 Jun 15.
Older kidney transplant recipients experience increased rates of infection and death, and less rejection, compared with younger patients. However, little is known about immune dysfunction in older compared with younger kidney transplant recipients and whether it is associated with infection. We evaluated T cell phenotypes including maturation, immune senescence, and exhaustion in a novel investigation into differences in older compared with younger patients receiving identical immune suppression regimens. We evaluated PBMC from 60 kidney transplant recipients (23 older and 37 matched younger patients) by multiparameter immune phenotyping. Older kidney transplant recipients demonstrated decreased frequency of naïve CD4+ and CD8+ T cells, and increased frequency of terminally differentiated, immune senescent, and NK T cells expressing KLRG1. There was a trend towards increased frequency of T cell immune senescence in patients experiencing infection in the first year after transplantation, which reached statistical significance in a multivariate analysis. This pilot study reveals immune dysfunction in older compared with younger transplant recipients, and suggests a likely mechanism for increased vulnerability to infection. The ability to assess T cell maturation and immune senescence in transplant recipients offers the potential for risk stratification and customization of immune suppression to prevent infection and rejection after transplantation.
与年轻患者相比,老年肾移植受者感染率和死亡率增加,排斥反应减少。然而,与年轻肾移植受者相比,老年患者免疫功能障碍情况以及其是否与感染相关却知之甚少。在一项针对接受相同免疫抑制方案的老年与年轻患者差异的全新研究中,我们评估了T细胞表型,包括成熟度、免疫衰老和耗竭情况。我们通过多参数免疫表型分析评估了60例肾移植受者(23例老年患者和37例匹配的年轻患者)的外周血单个核细胞(PBMC)。老年肾移植受者表现出初始CD4+和CD8+ T细胞频率降低,以及表达KLRG1的终末分化、免疫衰老和自然杀伤T细胞频率增加。移植后第一年发生感染的患者中,T细胞免疫衰老频率有增加趋势,在多变量分析中达到统计学意义。这项初步研究揭示了老年与年轻移植受者相比存在免疫功能障碍,并提示了感染易感性增加的可能机制。评估移植受者T细胞成熟度和免疫衰老的能力为风险分层以及定制免疫抑制方案以预防移植后感染和排斥反应提供了可能性。