Goldsmith N K, Dikman S, Bermas B, Davies T F, Roman S H
Department of Medicine, Mount Sinai School of Medicine, New York 10029.
Clin Immunol Immunopathol. 1988 Aug;48(2):161-73. doi: 10.1016/0090-1229(88)90080-3.
To further understand the relationship between the immune system and the neoplastic human thyroid cell we investigated the degree of intrathyroidal lymphocytic infiltration and thyroid HLA class II expression in 17 patients with thyroid tumors. In another 60 thyroid tumor patients the association of thyroidal lymphocytic infiltration with thyroid autoantibody production was analyzed. In total 117 thyroid tissues were examined including tissue obtained at autopsy (n = 28), fetal thyroid tissue (n = 4), thyroid samples obtained from areas distant from benign follicular adenomas (n = 5), and 80 abnormal thyroids including patients with benign (n = 53) or malignant (n = 24) thyroid tumors and Hashimoto's thyroiditis (n = 3). Normal adult and fetal thyroid tissue had no significant lymphocytic infiltration and no detectable HLA-DR, -DP, or -DQ antigens on their thyroid follicular epithelial cells. The degree of lymphocytic infiltration in the nonneoplastic thyroid tissue of thyroid glands with benign and malignant thyroid tumors varied considerably and correlated with the presence and titer of serum thyroid autoantibodies measured by sensitive ELISA techniques. However, all but one of the benign follicular adenomas had thyroid cells negative for HLA class II determinants despite the presence of infiltrating lymphocytes, while 7 of 10 thyroid carcinomas expressed class II antigen (principally HLA-DR) even when only minor degrees of lymphocytic infiltration were present. These data indicate a correlation between lymphocytic infiltrates and serum thyroid autoantibody titers but the relationship with HLA class II expression is more complex. Since we have previously shown that HLA class II antigen expression can be induced by local interferon-gamma secretion, presumably from activated T cells, we conclude that estimates of simple thyroid lymphocytic infiltration and serum autoantibody secretion do not correlate with the degree of intrathyroidal T-cell activation. Furthermore, our observation of increased expression of HLA class II antigens in thyroid cancer suggests considerable cellular heterogeneity in susceptibility to HLA class II antigen induction in human thyroid disease.
为了进一步了解免疫系统与人类甲状腺肿瘤细胞之间的关系，我们研究了17例甲状腺肿瘤患者甲状腺内淋巴细胞浸润程度及甲状腺HLA - II类抗原表达情况。另外，对60例甲状腺肿瘤患者分析了甲状腺淋巴细胞浸润与甲状腺自身抗体产生之间的关联。总共检查了117份甲状腺组织，包括尸检获得的组织（n = 28）、胎儿甲状腺组织（n = 4）、取自远离良性滤泡性腺瘤区域的甲状腺样本（n = 5），以及80份异常甲状腺组织，包括患有良性（n = 53）或恶性（n = 24）甲状腺肿瘤以及桥本甲状腺炎（n = 3）的患者。正常成人及胎儿甲状腺组织无明显淋巴细胞浸润，其甲状腺滤泡上皮细胞上未检测到HLA - DR、- DP或 - DQ抗原。良性和恶性甲状腺肿瘤患者甲状腺非肿瘤组织中的淋巴细胞浸润程度差异很大，且与采用敏感ELISA技术检测的血清甲状腺自身抗体的存在及滴度相关。然而，除1例良性滤泡性腺瘤外，尽管有浸润淋巴细胞存在，但所有良性滤泡性腺瘤的甲状腺细胞HLA - II类决定簇均为阴性，而10例甲状腺癌中有7例即使仅存在轻微程度的淋巴细胞浸润也表达II类抗原（主要是HLA - DR）。这些数据表明淋巴细胞浸润与血清甲状腺自身抗体滴度之间存在相关性，但与HLA - II类抗原表达的关系更为复杂。由于我们之前已表明HLA - II类抗原表达可由局部γ干扰素分泌诱导，推测来自活化的T细胞，因此我们得出结论，单纯的甲状腺淋巴细胞浸润估计值和血清自身抗体分泌与甲状腺内T细胞活化程度无关。此外，我们观察到甲状腺癌中HLA - II类抗原表达增加，这表明在人类甲状腺疾病中，对HLA - II类抗原诱导的易感性存在相当大的细胞异质性。
