Cell-Mediated Cytotoxicity in Lyme Arthritis.
Cell-Mediated Cytotoxicity in Lyme Arthritis.
复制标题
莱姆关节炎中细胞介导的细胞毒性。
DOI：
10.1002/art.42408
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Steere,AllenC
中科院分区：
文献类型：
--
作者：
Ordóñez,David;Lochhead,RobertB;Strle,Klemen;Pianta,Annalisa;Arvikar,Sheila;VanRhijn,Ildiko;Stemmer-Rachamimov,Anat;Steere,AllenC
目的约50%的抗生素后莱姆病（LA）患者滑膜组织存在闭塞性微血管病变，并与某些血管抗原的自身抗体相关。在这项研究中，我们发现具有细胞毒性潜能的淋巴细胞也可能介导滑膜病理的这一特征。方法采用抗生素反应性或抗生素后LA患者外周血单个核细胞（PBMCs）和滑液单个核细胞（SFMCs）样本检测淋巴细胞的细胞毒潜能及其T细胞受体（TCR） v β基因的使用。采用流式细胞术和细胞内细胞因子染色分析细胞表型。对抗生素后滑膜组织样本进行免疫组化。结果在SFMC和PBMC样本中，22例抗生素后LA患者的CD8+ T细胞和双阴性T细胞（主要是γδ T细胞）的百分比高于14例抗生素反应性LA患者。此外，CD8+ T细胞和γδ T细胞经常表达细胞毒性介质、颗粒酶A/颗粒酶B和穿孔素。同样的3个TCR v β片段在来自抗生素后LA患者的SFMC样本的CD4+ T细胞和CD8+ T细胞中都过度代表。在3例抗生素后LA患者的滑膜组织样本中，血管周围可见CD8+ T细胞与CD4+ T细胞混合，2例微血管损伤患者存在血管相关抗原的自身抗体。2例患者中有1例细胞毒性表现活跃，在闭塞血管上有补体（C5b-9）沉积。很少见自然杀伤细胞或γδ T细胞。结论CD8+ T细胞介导的细胞毒性、CD4+ T细胞帮助、针对血管抗原的自身抗体和补体沉积都可能在抗生素后LA的微血管损伤中发挥作用。
ObjectiveObliterative microvascular lesions are found in the synovial tissue of ~50% of patients with post‐antibiotic Lyme arthritis (LA) and correlate with autoantibodies to certain vascular antigens. In this study, we identified lymphocytes with cytotoxic potential that may also mediate this feature of synovial pathology.MethodsThe cytotoxic potential of lymphocytes and their T cell receptor (TCR) Vβgene usage were determined using samples of peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with antibiotic‐responsive or post‐antibiotic LA. Cell phenotypes were analyzed using flow cytometry and intracellular cytokine staining. Immunohistochemistry was performed on post‐antibiotic synovial tissue samples.ResultsIn SFMC and PBMC samples, the percentages of CD8+ T cells and double‐negative T cells (primarily γδ T cells) were greater among 22 patients with post‐antibiotic LA than in 14 patients with antibiotic‐responsive LA. Moreover, CD8+ T cells and γδ T cells often expressed cytotoxic mediators, granzyme A/granzyme B, and perforin. The same 3 TCR Vβsegments were over‐represented in both CD4+ T cells and CD8+ T cells in SFMC samples from post‐antibiotic LA patients. In synovial tissue samples from 3 patients with post‐antibiotic LA, CD8+ T cells intermixed with CD4+ T cells were seen around blood vessels, and 2 patients with microvascular damage had autoantibodies to vascular‐associated antigens. One of these 2 patients, the one in whom cytotoxicity appeared to be active, had complement (C5b–9) deposition on obliterated vessels. Very few natural killer cells or γδ T cells were seen.ConclusionWe propose that CD8+ T cell–mediated cytotoxicity, CD4+ T cell help, autoantibodies to vascular antigens, and complement deposition may each have a role in microvasculature damage in post‐antibiotic LA.