Pitzalis C, Cauli A, Pipitone N, Smith C, Barker J, Marchesoni A, Yanni G, Panayi G S
United Medical and Dental Schools of Guy's Hospital, London, England.
Arthritis Rheum. 1996 Jan;39(1):137-45. doi: 10.1002/art.1780390118.
To investigate whether T cell migration into different sites of inflammation (skin and synovium) within the same individual is principally regulated by tissue-specific homing or by more general mechanisms related to inflammation.
Expression of cutaneous lymphocyte antigen (CLA) and its ligand, E-selectin, was analyzed by immunohistochemistry and immunofluorescence using paired skin and synovial membrane (SM) samples from patients with psoriatic arthritis (PsA). To investigate disease specificity, delayed-type hypersensitivity (DTH) skin lesions, induced by tuberculin purified protein derivative, and SM from patients with rheumatoid arthritis (RA), were studied as controls. To directly examine cell migration in in vivo, the proportion of CLA+ T lymphocytes migrating into suction-induced skin blisters was assessed by flow cytometry. Using the same technique, levels of paired peripheral blood and synovial fluid (SF) T cells were also analyzed.
CLA+ T cells preferentially accumulated in the skin, but not in the joint, of patients with PsA. Similarly, CLA+ T lymphocytes predominated in the DTH skin lesions of RA patients, but were very rare in the SM of RA patients, and were scarcely represented in the SF of patients with several chronic inflammatory arthropathies. In addition, CLA+ T lymphocytes preferentially migrated into epidermal skin blisters. This preferential pattern of CLA+ T cell accumulation was not related to the selective expression of E-selectin, since this was similar in the skin and SM of both PsA and RA patients.
The distinct pattern of T cell infiltration into sites of inflammation within the skin and synovium is regulated by both organ-specific homing and general inflammation-related mechanisms.
研究在同一个体中,T细胞迁移至不同炎症部位(皮肤和滑膜)主要是受组织特异性归巢调控,还是受与炎症相关的更普遍机制调控。
采用免疫组织化学和免疫荧光法,对银屑病关节炎(PsA)患者的配对皮肤和滑膜样本进行分析,检测皮肤淋巴细胞抗原(CLA)及其配体E-选择素的表达。为研究疾病特异性,以结核菌素纯蛋白衍生物诱导的迟发型超敏反应(DTH)皮肤损伤以及类风湿关节炎(RA)患者的滑膜作为对照进行研究。为直接检测体内细胞迁移情况,采用流式细胞术评估迁移至负压吸引诱导的皮肤水疱中的CLA+ T淋巴细胞比例。运用相同技术,还分析了配对的外周血和滑液(SF)T细胞水平。
PsA患者中,CLA+ T细胞优先聚集在皮肤而非关节。同样,CLA+ T淋巴细胞在RA患者的DTH皮肤损伤中占主导,但在RA患者的滑膜中非常罕见,在几种慢性炎症性关节病患者的滑液中也几乎没有。此外,CLA+ T淋巴细胞优先迁移至表皮皮肤水疱。CLA+ T细胞这种优先聚集模式与E-选择素的选择性表达无关,因为在PsA和RA患者的皮肤和滑膜中,E-选择素的表达情况相似。
T细胞浸润至皮肤和滑膜内炎症部位的不同模式,受器官特异性归巢和与炎症相关的普遍机制共同调控。