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格雷夫斯病患者外周血和甲状腺来源淋巴细胞的不同免疫表型及自身抗体产生情况

Different immunophenotype and autoantibody production by peripheral blood and thyroid-derived lymphocytes in patients with Graves' disease.

作者信息

Aust G, Lehmann I, Heberling H J

机构信息

Department of Internal Medicine III, University of Leipzig, Germany.

出版信息

Exp Clin Endocrinol Diabetes. 1996;104(1):50-8. doi: 10.1055/s-0029-1211422.

DOI:10.1055/s-0029-1211422
PMID:8750571
Abstract

Direct multi-colour flow cytometric analysis was employed in patients with Graves' disease (n = 10) to determine the immunophenotype in peripheral blood lymphocytes (PBL) at the time of diagnosis without treatment (PBLw) and prior to operation (PBLp) and in thyroid-derived lymphocytes (TL). Additionally, the secretion of anti-thyroperoxidase antibodies (anti-TPO) was measured during culture of isolated peripheral or thyroid-derived B cells. Among TL from patients with high serum levels of anti-TPO (6/10) a significantly (p < 0.01) higher percentage of B cells were detected compared to PBLp (TL: 21.7 +/- 7.2%; PBLp: 13.2 +/- 4.5%). Enriched thyroid-derived B cells only from these patients also showed high spontaneous anti-TPO secretion during culture. The difference between peripheral and thyroid-derived natural killer (NK) cells was highly significant (p < 0.001; TL: 5.6 +/- 6.3%; PBLp: 13.6 +/- 5.5%). Two patients were found with a higher number of NK cells within TL. These patients were among those who had a low number of B cells infiltrating the thyroid gland. Regarding the expression of several other differentiation antigens, i.e. CD4 and CD8, gamma/delta TCR bearing T cells and CD45R0 on CD4+ T cells as a marker for memory cells, on TL no differences could be detected between patients with or without anti-TPO. In TL 31.5 +/- 7.7% of CD3- cells expressed the HLA-DR antigen (vs. 6.1 +/- 2.4% in PBLp; p < 0.001). Half of these cells simultaneously expressed the activation antigen CD69. Surprisingly, the number of CD3+ TL bearing the IL-2 receptor (CD25) and transferrin receptor (CD71) was not increased. Taken together, the proportional distribution of B and NK cells within the thyroid correlates with the anti-TPO secretion in vivo and in vitro, suggesting different immune response regulation processes of TL.

摘要

对10例格雷夫斯病患者进行直接多色流式细胞术分析,以确定未经治疗的诊断时(PBLw)、手术前(PBLp)外周血淋巴细胞(PBL)以及甲状腺来源淋巴细胞(TL)的免疫表型。此外,在分离的外周或甲状腺来源B细胞培养期间测量抗甲状腺过氧化物酶抗体(抗TPO)的分泌。在抗TPO血清水平高的患者(6/10)的TL中,与PBLp相比,检测到的B细胞百分比显著更高(p < 0.01)(TL:21.7 +/- 7.2%;PBLp:13.2 +/- 4.5%)。仅来自这些患者的富集甲状腺来源B细胞在培养期间也显示出高自发抗TPO分泌。外周和甲状腺来源的自然杀伤(NK)细胞之间的差异非常显著(p < 0.001;TL:5.6 +/- 6.3%;PBLp:13.6 +/- 5.5%)。发现2例患者的TL中NK细胞数量较多。这些患者属于甲状腺中浸润B细胞数量较少的患者。关于其他几种分化抗原的表达,即CD4和CD8、携带γ/δTCR的T细胞以及作为记忆细胞标志物的CD4 + T细胞上的CD45R0,在有或没有抗TPO的患者的TL之间未检测到差异。在TL中,31.5 +/- 7.7%的CD3 - 细胞表达HLA - DR抗原(相比之下,PBLp中为6.1 +/- 2.4%;p < 0.001)。这些细胞中有一半同时表达激活抗原CD69。令人惊讶的是,携带白细胞介素 - 2受体(CD25)和转铁蛋白受体(CD71)的CD3 + TL数量没有增加。总之,甲状腺内B细胞和NK细胞的比例分布与体内和体外抗TPO分泌相关,提示TL存在不同的免疫反应调节过程。

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