Kowli Sangeeta, Minocherhomji Sheroy, Martinez Olivia M, Busque Stephan, Lebrec Herve, Maecker Holden T
Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, United States.
Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA, United States.
Immunohorizons. 2025 Feb 18;9(4). doi: 10.1093/immhor/vlae013.
Chronic immunosuppressive therapies are crucial in organ transplantation but can increase the risk of opportunistic infections and cancer over time. We investigated immune status changes in 10 kidney transplant patients and 11 age-matched healthy adults using broad in vitro stimulation of subject-derived peripheral blood mononuclear cells followed by mass cytometry by time of flight over 6 mo. Overall, the immune cells of transplant patients exhibited increased CD8+ T cell activation and differentiation compared with healthy donors, with elevated CD8+ CD57+, MIP-1β, and interferon γ production (P < 0.05, P < 0.05, and P < 0.01, respectively). CD107a and granzyme B expression were increased in CD8+ T cells and CD56bright natural killer cells (P < 0.05 and P < 0.01, respectively), while T regulatory cells had decreased interleukin-10 production (P < 0.05). These changes indicated a proinflammatory environment influenced by induction therapy and ongoing maintenance drugs. Additionally, transplant recipients displayed signs of immune modulation, including decreased tumor necrosis factor α, interferon γ, and MIP-1β expression in γδT cells (P < 0.05 and P < 0.01), and reduced interleukin-17 and granulocyte-macrophage colony-stimulating factor expression in CD8+ T memory cell subsets (P < 0.05). The diverse functional changes underscore the importance of comprehensive immune status profiling for optimizing individual treatment strategies and developing better immunosuppressants that specifically target activated cell populations.
慢性免疫抑制疗法在器官移植中至关重要,但随着时间的推移会增加机会性感染和癌症的风险。我们对10名肾移植患者和11名年龄匹配的健康成年人进行了免疫状态变化调查,在6个月的时间里,对受试者来源的外周血单个核细胞进行广泛的体外刺激,然后通过飞行时间质谱流式细胞术进行检测。总体而言,与健康供体相比,移植患者的免疫细胞表现出CD8 + T细胞活化和分化增加,CD8 + CD57 +、MIP - 1β和干扰素γ的产生升高(分别为P < 0.05、P < 0.05和P < 0.01)。CD8 + T细胞和CD56bright自然杀伤细胞中CD107a和颗粒酶B的表达增加(分别为P < 0.05和P < 0.01),而调节性T细胞的白细胞介素-10产生减少(P < 0.05)。这些变化表明诱导治疗和持续维持药物影响下的促炎环境。此外,移植受者表现出免疫调节迹象,包括γδT细胞中肿瘤坏死因子α、干扰素γ和MIP - 1β表达降低(P < 0.05和P < 0.01),以及CD8 + T记忆细胞亚群中白细胞介素-17和粒细胞-巨噬细胞集落刺激因子表达降低(P < 0.05)。这些多样的功能变化强调了全面免疫状态分析对于优化个体治疗策略和开发专门针对活化细胞群体的更好免疫抑制剂的重要性。