The in vitro regulation of human thyrocyte HLA-DR antigen expression.

The in vitro regulation of human thyrocyte HLA-DR antigen expression.
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人甲状腺细胞HLA-DR抗原表达的体外调节。

DOI:
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发表时间:
1985
影响因子:
5.8
通讯作者:
A. Fauci
A. Fauci
中科院分区:
医学2区
文献类型:
--
作者:
A. Weetman;D. Volkman;K. Burman;T. Gerrard;A. Fauci

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内分泌器官表达人类免疫应答相关抗原(Ia)(如HLA-DR)的能力是当前强烈关注的主题。在这项研究中,甲状腺滤泡细胞HLA-DR表达的各种潜在的调制器的影响进行了研究,使用体外培养。含有T细胞来源的淋巴因子的培养上清液导致13-18%的甲状腺细胞表达DR抗原;重组γ-干扰素产生更一致的效果,导致46-100%的甲状腺细胞在培养3天后成为HLA-DR阳性。这种效应具有时间和浓度依赖性,并且发生在来自Graves病(n = 7)和桥本甲状腺炎(n = 2)患者以及三名无自身免疫性甲状腺疾病的受试者的甲状腺细胞中。甲状腺细胞用单克隆抗体4F 2和5E 9染色,这些抗体识别细胞活化抗原,而不管它们是否用γ-干扰素处理。植物凝集素还诱导HLA-DR抗原表达(21-91%的细胞阳性)。这种反应依赖于甲状腺细胞悬液的T细胞污染,因为这种作用被环孢菌素A抑制。由Leu-10单克隆抗体鉴定的HLA-DQ抗原表达也由γ-干扰素和植物血凝素在甲状腺细胞上诱导。相反,重组α-干扰素和白细胞介素-2都不能诱导HLA-DR抗原。辐射降低甲状腺细胞对γ-干扰素的反应,但两种已知的巨噬细胞Ia表达抑制剂,前列腺素E2和(Bu)2cAMP,不影响γ-干扰素诱导的甲状腺细胞HLA-DR表达。我们无法检测到甲状腺细胞产生白细胞介素-1。这些结果表明:1)在正常情况下,甲状腺细胞是4F 2和5E 9阳性的,但不能表达Ia抗原,因此不能激活T细胞以引发自身免疫性甲状腺炎; 2)一旦被激活,例如被病毒激活,T细胞可以释放γ-干扰素并诱导甲状腺细胞HLA-DR和-DQ抗原表达;这些Ia阳性甲状腺细胞则可在维持或增强自身免疫应答中起作用。
The ability of endocrine organs to express human immune response-associated antigens (Ia), such as HLA-DR, is a subject of intense current interest. In this study, the effects of various potential modulators of thyroid follicular cell HLA-DR expression were examined using in vitro cultures. A culture supernatant containing T-cell-derived lymphokines caused DR antigen expression on 13-18% of thyroid cells; more consistent effects were produced by recombinant gamma-interferon, which led to 46-100% of the thyroid cells becoming HLA-DR positive after 3 days in culture. This effect was both time and concentration dependent and occurred in thyroid cells derived from patients with Graves' disease (n = 7) and Hashimoto's thyroiditis (n = 2) as well as from three subjects with no autoimmune thyroid disease. Thyroid cells stained with the monoclonal antibodies 4F2 and 5E9, which recognize cell activation antigens, regardless of whether they were treated with gamma-interferon. The lectin phytohemagglutinin also induced HLA-DR antigen expression (21-91% of cells positive). This response was dependent on T cell contamination of thyroid cell suspensions, since the effect was inhibited by cyclosporin A. HLA-DQ antigen expression, identified by the Leu-10 monoclonal antibody, was also induced on thyroid cells by gamma-interferon and phytohemagglutinin. In contrast, neither recombinant alpha-interferon nor interleukin-2 induced HLA-DR antigens. Irradiation reduced the response of thyroid cells to gamma-interferon, but two of the known inhibitors of macrophage Ia expression, prostaglandin E2 and (Bu)2cAMP, did not affect gamma-interferon-induced thyroid cell HLA-DR expression. We were unable to detect interleukin-1 production by thyroid cells. These results suggest that 1) under normal circumstances, thyroid cells are 4F2 and 5E9 positive, but are incapable of expressing Ia antigens and, thus, of activating T cells to initiate autoimmune thyroiditis; and 2) once activated, for example by a virus, T cells could release gamma-interferon and induce thyroid cell HLA-DR and -DQ antigen expression; these Ia-positive thyroid cells could then have a role in maintaining or enhancing the autoimmune response.
定义细胞活化的人细胞表面抗原的单克隆抗体 (5E9) 的表征。
DOI: --
发表时间: 1981
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Haynes,BF;Hemler,M;Cotner,T;Mann,DL;Eisenbarth,GS;Strominger,JL;Fauci,AS
通讯作者: Fauci,AS