Taplits M S, Henkart P A, Hodes R J
Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1988 Jul 1;141(1):1-9.
A series of class II MHC-restricted keyhole limpet hemocyanin-specific Th cell clones were examined for cytoplasmic granules by histochemical techniques and fractionation of their homogenates. All showed granules containing lysosomal enzymes and high levels of trypsin-like activity revealed by a N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester-esterase assay. Using the latter as a marker for granule contents, granule secretion was observed in response to MHC-restricted, Ag-dependent signals presented in vitro, and correlated well with T cell activation as measured by proliferation. However, human rIL-2, a strong inducer of T cell proliferation, did not stimulate N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester-esterase secretion by itself, nor did it influence the secretion mediated by Ag. Other factors found to induce secretion included immobilized antibodies directed against determinants of the TCR complex, as well as Con A. These results suggest that granule enzyme secretion is another indicator of TCR-mediated activation and provides a possible mechanism for Th cell function via a rapid, local delivery of granule contents to adjacent cells.
通过组织化学技术和匀浆分级分离,对一系列Ⅱ类主要组织相容性复合体(MHC)限制的钥孔戚血蓝蛋白特异性Th细胞克隆进行了细胞质颗粒检查。所有克隆均显示含有溶酶体酶的颗粒,并且通过N-α-苄氧羰基-L-赖氨酸硫代苄酯酯酶测定显示出高水平的胰蛋白酶样活性。以后者作为颗粒内容物的标志物,观察到在体外呈现的MHC限制的、抗原依赖性信号刺激下颗粒分泌,并且与通过增殖测定的T细胞活化密切相关。然而,人重组白细胞介素-2(rIL-2)作为T细胞增殖的强诱导剂,自身并不刺激N-α-苄氧羰基-L-赖氨酸硫代苄酯酯酶分泌,也不影响抗原介导的分泌。发现诱导分泌的其他因素包括针对T细胞受体(TCR)复合体决定簇的固定化抗体以及刀豆蛋白A(Con A)。这些结果表明颗粒酶分泌是TCR介导的活化的另一个指标,并通过将颗粒内容物快速、局部递送至相邻细胞为Th细胞功能提供了一种可能的机制。