IL-12 receptor. II. Distribution and regulation of receptor expression.
IL-12 receptor. II. Distribution and regulation of receptor expression.
复制标题
IL-12 受体。
作者：
B. Desai;P. Quinn;A. G. Wolitzky;P. Mongini;R. Chizzonite;M. Gately
IL-12是一种异二聚体淋巴因子，其诱导静息PBMC产生IFN-γ，增强NK/淋巴因子激活的杀伤细胞的溶解活性，并引起激活的T细胞和NK细胞的增殖。在这份报告中，我们研究了IL-12 R的表达对丝裂原和IL-2激活的PBMC或扁桃体淋巴细胞以及各种细胞系。放射性标记的IL-12结合测定的结果表明，高亲和力IL-12 R存在于由各种T细胞有丝分裂原或IL-2激活的PBMC上。还发现高亲和力IL-12 R在转化的绒猴NK样细胞系HVS.SILVA 40上组成型表达。在峰值IL-12 R表达时，促分裂原或IL-2活化的细胞显示约1000至9000个IL-12结合位点/细胞，表观Kd为100至900 pM。动力学研究显示，与IL-2激活的PBMC相比，PHA激活的PBMC上IL-12 R的最大表达发生得更早，并且这些细胞上IL-12 R的表达与它们响应IL-12的增殖能力相关。虽然IL-2可以上调IL-12 R在静息PBMC上的表达，但发现丝裂原活化的PBMC上调IL-12 R的能力不依赖于IL-2。通过流式细胞术分析IL-12 R表达揭示IL-12的受体存在于活化的CD 4+和CD 8+亚群的T细胞上以及活化的CD 56 + NK细胞上。相反，无论是静止的PBMC或扁桃体B细胞，还是由抗IgM/Dx、抗IgM/Dx + IL-2或SAC + IL-2激活的扁桃体B细胞，都不显示通过流式细胞术或通过放射性标记的IL-12结合测定可检测到的IL-12 R。总之，这些结果表明T细胞或NK细胞的活化导致IL-12 R表达的上调;另一方面，B细胞活化，至少在某些情况下，似乎与IL-12 R表达的增强无关。
IL-12 is a heterodimeric lymphokine that induces IFN-gamma production by resting PBMC, enhances the lytic activity of NK/lymphokine activated killer cells, and causes the proliferation of activated T cells and NK cells. In this report, we have investigated the expression of IL-12R on mitogen- and IL-2-activated PBMC or tonsillar lymphocytes as well as on a variety of cell lines. The results of radiolabeled IL-12-binding assays indicated that high affinity IL-12R are present on PBMC activated by various T cell mitogens or by IL-2. High affinity IL-12R were also found to be expressed constitutively on a transformed marmoset NK-like cell line HVS.SILVA 40. At the time of peak IL-12R expression, mitogen- or IL-2-activated cells displayed approximately 1000 to 9000 IL-12 binding sites/cell with an apparent Kd of 100 to 900 pM. Kinetic studies revealed that maximum expression of IL-12R occurred earlier on PHA-activated PBMC as compared with PBMC activated by IL-2, and that expression of IL-12R on these cells correlated with their ability to proliferate in response to IL-12. Although IL-2 could up-regulate IL-12R expression on resting PBMC, the ability of mitogen-activated PBMC to up-regulate IL-12R was found to be independent of IL-2. Analysis of IL-12R expression by flow cytometry revealed that receptors for IL-12 are present on activated T cells of both the CD4+ and CD8+ subsets and on activated CD56+ NK cells. In contrast, neither resting PBMC or tonsillar B cells nor tonsillar B cells activated by anti-IgM/Dx, anti-IgM/Dx + IL-2, or SAC + IL-2 displayed IL-12R detectable by flow cytometry or by the radiolabeled IL-12-binding assay. In summary, these results indicate that activation of T cells or NK cells results in up-regulation of IL-12R expression; on the other hand, B cell activation, at least under some circumstances, appears not to be associated with enhanced expression of IL-12R.