Symington F W, Santos E B
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
J Immunol. 1991 Apr 1;146(7):2169-75.
Exposure of human KC to IFN-gamma increases their susceptibility to lysis by CTL. The mechanism of this enhanced lysis was investigated by analyzing interactions of IFN-gamma-treated and nontreated cultured KC with allogeneic class I-specific CTL clones. rIFN-gamma treatment augmented KC lysis in a time- and dose-dependent manner. Increased lysis of IFN-KC was detected after only 2 h of IFN-gamma treatment and was maximal by 12 h. Enhanced lysis of IFN-KC was Ag-specific, inasmuch as nonantigenic IFN-KC were not lysed either directly or as bystanders during the lysis of antigenic KC. Parallel immunofluorescence and cytotoxicity assays of KC treated with IFN-gamma for various intervals revealed a direct correlation between the degree of increased KC lysis and levels of cell surface ICAM-1 (CD54), but not of specific alloantigen or beta 2-microglobulin. Lysis of nontreated KC was blocked by mAb against class I or CD3, but not by mAb against ICAM-1 or LFA-1. In contrast, lysis of IFN-KC was partially inhibited by anti-ICAM-1 or anti-LFA-1 mAb, but resisted inhibition by anti-class I mAb except in the presence of anti-ICAM-1. These results indicate that both ICAM-1/LFA-1 and Ag/CD3-TcR interactions are important for Ag-specific lysis of IFN-KC, whereas lysis of nontreated KC depends on Ag/CD3-TcR but not ICAM-1/LFA-1 interactions. Equivalent inhibition of IFN-KC lysis by mAb against ICAM-1 or LFA-1 suggests that ICAM-1 is the only LFA-1 ligand involved in enhanced IFN-KC lysis. Furthermore, enhanced CTL lysis of KC after short-term IFN-gamma treatment can be explained solely on the basis of ICAM-1 induction, because all of the increase in specific lysis associated with IFN-gamma treatment could be blocked by mAb that block ICAM-1/LFA-1 interactions.
人角质形成细胞（KC）暴露于γ干扰素（IFN-γ）会增加其对细胞毒性T淋巴细胞（CTL）裂解的敏感性。通过分析经IFN-γ处理和未经处理的培养KC与同种异体I类特异性CTL克隆之间的相互作用，研究了这种增强裂解的机制。重组IFN-γ处理以时间和剂量依赖的方式增强了KC的裂解。仅在IFN-γ处理2小时后就检测到IFN-KC的裂解增加，并在12小时时达到最大值。IFN-KC的增强裂解具有抗原特异性，因为在抗原性KC裂解期间，非抗原性IFN-KC既不会被直接裂解，也不会作为旁观者被裂解。对用IFN-γ处理不同时间间隔的KC进行平行免疫荧光和细胞毒性测定，结果显示KC裂解增加的程度与细胞表面细胞间黏附分子-1（ICAM-1，CD54）水平之间存在直接相关性，但与特异性同种异体抗原或β2-微球蛋白水平无关。未处理KC的裂解可被抗I类或抗CD3单克隆抗体阻断，但不能被抗ICAM-1或抗淋巴细胞功能相关抗原-1（LFA-1）单克隆抗体阻断。相反，IFN-KC的裂解可被抗ICAM-1或抗LFA-1单克隆抗体部分抑制，但除了存在抗ICAM-1的情况下，抗I类单克隆抗体不能抑制其裂解。这些结果表明，ICAM-1/LFA-1和抗原/CD3-T细胞受体（TcR）相互作用对于IFN-KC的抗原特异性裂解都很重要，而未处理KC的裂解取决于抗原/CD3-TcR相互作用，而非ICAM-1/LFA-1相互作用。抗ICAM-1或抗LFA-1单克隆抗体对IFN-KC裂解的等效抑制表明，ICAM-1是参与增强IFN-KC裂解的唯一LFA-1配体。此外，短期IFN-γ处理后CTL对KC裂解的增强仅基于ICAM-1的诱导就可以解释，因为与IFN-γ处理相关的特异性裂解的所有增加都可以被阻断ICAM-1/LFA-1相互作用的单克隆抗体阻断。
