The balance between memory and regulatory cell populations in kidney transplant recipients with operational tolerance.

IF 3.4 3区 医学 Q3 IMMUNOLOGY Clinical and experimental immunology Pub Date : 2024-05-16 DOI:10.1093/cei/uxae018
Caner Süsal, Cristiam M Alvarez, Louise Benning, Volker Daniel, Martin Zeier, Matthias Schaier, Christian Morath, Claudius Speer
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Abstract

Donor-reactive memory cells represent a barrier to long-term kidney graft survival. A better understanding of regulatory mechanisms that counterbalance alloreactive memory responses may help to identify patients with operational tolerance. This prospective study investigated the equilibrium between memory T-cell subsets and regulatory T or B cells (Tregs, Bregs) in peripheral blood of kidney transplant recipients with operational tolerance (N = 8), chronic rejection (N = 8), and different immunosuppressive treatment regimens (N = 81). Patients on hemodialysis and healthy individuals served as controls (N = 50). In addition, the expression of Treg- and Breg-associated molecule genes was analyzed. Patients with chronic rejection showed a disrupted memory T-cell composition with a significantly higher frequency of circulating CD8+ terminally differentiated effector memory (TEMRA) T cells than patients with operational tolerance, patients on hemodialysis, or healthy controls (P < 0.001). Low frequency of CD8+ TEMRA and high frequency of Tregs and transitional Bregs were found in operationally tolerant patients. Consequently, operationally tolerant patients showed, as compared to all other transplant recipients with different immunosuppressive regiments, the lowest ratios between CD8+ TEMRA T cells and Tregs or Bregs (for both P < 0.001). Moreover, a specific peripheral blood transcription pattern was found in operationally tolerant patients with an increased expression of Breg- and Treg-associated genes CD22 and FoxP3 and a decreased FcγRIIA/FcγRIIB transcript ratio (for all P < 0.001). In conclusion, monitoring the balance between circulating CD8+ TEMRA T cells and regulatory cell subsets and their transcripts may help to distinguish transplant recipients with operational tolerance from recipients at risk of graft loss.

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肾移植受者中具有操作耐受性的记忆细胞群和调节细胞群之间的平衡。
捐献者反应性记忆细胞是肾移植长期存活的障碍。更好地了解平衡异体反应性记忆反应的调节机制可能有助于识别具有操作耐受性的患者。这项前瞻性研究调查了肾移植受者外周血中记忆性T细胞亚群与调节性T细胞或B细胞(Tregs、Bregs)之间的平衡关系,这些受者分别具有操作耐受性(8例)、慢性排斥反应(8例)和不同的免疫抑制治疗方案(81例)。血液透析患者和健康人作为对照(50 人)。此外,还分析了Treg和Breg相关分子基因的表达。慢性排斥反应患者的记忆T细胞组成紊乱,循环中CD8+终末分化效应记忆(TEMRA)T细胞的频率明显高于操作耐受患者、血液透析患者或健康对照组(P<0.05)。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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