Involvement of both Tac and non-Tac interleukin 2-binding peptides in the interleukin 2-dependent proliferation of human tumor-infiltrating lymphocytes.
Involvement of both Tac and non-Tac interleukin 2-binding peptides in the interleukin 2-dependent proliferation of human tumor-infiltrating lymphocytes.
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发表时间：
1989-03
期刊：
影响因子：
11.2
通讯作者：
M. Yagita;K. Itoh;M. Tsudo;L. B. Schaub;C. Platsoucas;C. Balch;E. Grimm
中科院分区：
文献类型：
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作者：
M. Yagita;K. Itoh;M. Tsudo;L. B. Schaub;C. Platsoucas;C. Balch;E. Grimm
研究了8例转移性黑色素瘤和3例肉瘤样本中IL-2 （IL-2）受体在重组IL-2 （IL-2）增殖的肿瘤浸润淋巴细胞（TIL）中的表达。所有11个TIL都以类似的增长率增长。在4至8周的培养期间，通过免疫荧光和流式细胞术多次检测，il -2从8个不含Tac抗原阳性淋巴细胞的转移性黑色素瘤标本中的5个中增殖TIL。然而，通过[125I]IL-2交联和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳检测，“tac阴性”TIL确实表达了非tac IL-2结合肽p70-75。IL-2结合试验显示，这些“tac阴性”TIL仅表达一种中等亲和力的IL-2受体。相比之下，通过流式细胞术分析，8例黑色素瘤中的另外3例和所有3例肉瘤的TIL中含有三分之一的Tac阳性细胞，并且通过[125I]IL-2交联表达表面非Tac （p70-75）和Tac （p55）肽。这些“tac阳性”TIL显示高亲和力和中等亲和力的IL-2受体。然而，“Tac阴性”和“Tac阳性”TIL的ril -2依赖性生长均被抗Tac单抗显著抑制，这表明Tac在“Tac阴性”TIL上有短暂表达。此外，由于我们的方法的局限性，我们不能排除低水平Tac的本构表达，高水平Tac的不可表达的可能性。将植物血凝素和肉豆酸酯phorbol刺激的外周血单核细胞培养上清加入48小时内Tac阴性的TIL诱导的可检测的Tac表达。这些结果表明，非Tac和Tac IL-2受体在TIL的IL-2依赖性增殖过程中发挥重要作用。
Interleukin 2 (IL-2) receptor expression was examined on recombinant IL-2 (rIL-2)-propagated tumor-infiltrating lymphocytes (TIL) from eight metastatic melanoma and three sarcoma samples. All 11 TIL expanded with similar growth rates. rIL-2 propagated TIL from five of eight metastatic melanoma specimens contained no Tac antigen-positive lymphocytes as determined by immunofluorescence and flow cytometry performed multiple times during the 4 to 8 week culture period. However, "Tac-negative" TIL did express the non-Tac IL-2-binding peptide, p70-75 as determined by [125I]IL-2 cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IL-2-binding assays revealed that these "Tac-negative" TIL expressed only an intermediate affinity IL-2 receptor. In contrast, TIL from the other three of eight melanoma and all three sarcoma contained one-third Tac-positive cells as assessed by flow cytometry analysis, and expressed surface non-Tac (p70-75) and Tac (p55) peptides by [125I]IL-2 cross-linking. These "Tac-positive" TIL displayed both the high and intermediate affinity IL-2 receptors. However, rIL-2-dependent growth of both "Tac-negative" and "Tac-positive" TIL was significantly inhibited by anti-Tac mAb, suggesting a transient Tac expression on the "Tac-negative" TIL. Additionally, due to the limits of our methodology, we cannot rule out the possibility of a constitutive expression of a low level of Tac, with an indicible expression of higher levels. Addition of culture supernatants from phytohemagglutinin- and phorbol myristate acetate-stimulated peripheral blood mononuclear cells to the "Tac-negative" TIL-induced detectable Tac expression within 48 h. These results indicate that both non-Tac and Tac IL-2 receptors play important roles during IL-2-dependent proliferation of TIL.