Interferon-gamma modulates HLA class II antigen expression on cultured human thymic epithelial cells.
Interferon-gamma modulates HLA class II antigen expression on cultured human thymic epithelial cells.
复制标题
干扰素-γ 调节培养的人胸腺上皮细胞上的 HLA II 类抗原表达。
作者：
S. Berrih;F. Arenzana‐Seisdedos;S. Cohen;R. Devos;D. Charron;J. Virelizier
用间接免疫荧光法检测培养的人胸腺上皮细胞(TEC)中HLAI类(A、B、C)和II类(DR、DC)抗原的表达。用抗角蛋白抗血清证实细胞的上皮性。在培养开始时，TEC高水平表达HLAI类抗原(接近100%阳性细胞)，并在12天内保持不变。相反，HLAII类抗原的表达(第2天为85%的DR+和75%的DC+)逐渐下降，到第7天达到非常低的水平(不到5%的DR+或DC+)。在含有干扰素-γ的活化T细胞培养上清液的存在下，这种II类抗原表达的丧失并不明显。此外，从培养开始就在培养上清液中加入重组干扰素-γ(r干扰素-γ)可维持大量细胞上的人类白细胞抗原-DR和DC抗原的表达(与培养第2天观察到的结果相当)。在rIFN-γ处理的细胞中，有很大比例的细胞胞浆内也有HLA-DR抗原的表达。在培养开始后的不同时间加入r干扰素-γ可重新诱导DR和DC抗原的表达。在低至10IU/ml的浓度下，这种效应在48小时内被观察到，并且明显是该干扰素物种所特有的，因为当浓度达到1000IU/ml时，r干扰素-α不能改变HLAII类抗原的表达。HLAII类抗原表达的增加真正是由于单个TEC的诱导，而不是对II类阳性细胞的选择，因为在干扰素-γ的影响下诱导是可逆的，并且在丝裂霉素处理或伽马辐射的培养中发生在没有增殖的情况下。我们的结果表明，干扰素-γ能促进培养的TEC合成和表达HLAII类抗原。这一发现提出了这样一种可能性，即干扰素-γ参与了确保在体内观察到的TEC中DR和DC抗原永久表达的机制，在自我认识教育方面具有潜在的重要作用。
Cultures of human thymic epithelial cells (TEC) were tested for the expression of HLA class I (A, B, C) and class II (DR and DC) antigens by indirect immunofluorescence. The epithelial nature of the cells was proven by using an antikeratin antiserum. A high level of expression (close to 100% positive cells) of HLA class I antigens was observed on TEC at the beginning of the culture and remained unchanged for up to 12 days. In contrast, HLA class II antigen expression (85% DR+ and 75% DC+ cells on day 2) decreased gradually and reached very low levels (less than 5% DR+ or DC+) by day 7 of culture. This loss of class II antigen expression was not seen when cultures were performed in the presence of supernatants from activated T cells containing interferon-gamma (IFN-gamma). Furthermore, the presence of recombinant IFN-gamma (rIFN-gamma) in the medium from the onset of culture maintained HLA-DR and DC antigen expression on a high number of cells (comparable to that observed on day 2 of culture). A large percentage of rIFN-gamma-treated cells also showed intracytoplasmic HLA-DR antigen expression. Addition of rIFN-gamma at various times after the onset of the culture led to a reinduction of DR and DC antigen expression. This effect of rIFN-gamma was observed in 48 hr with concentrations as low as 10 IU/ml and was apparently specific for this IFN species, in that rIFN-alpha was unable to modify HLA class II antigen expression at concentrations up to 1000 IU/ml. The increased expression of HLA class II antigen was truly due to induction in individual TEC, rather than selection of class II-positive cells, because induction under the influence of IFN-gamma was reversible and occurred in the absence of proliferation in mitomycin-treated or gamma-irradiated cultures. Our results indicate that synthesis and membrane expression of class II HLA antigens are enhanced by IFN-gamma in TEC cultures. This finding raises the possibility that IFN-gamma participates in the mechanisms that assure the permanent expression of DR and DC antigens observed in TEC in vivo, with potentially important functional consequences in terms of education for self recognition.