Mulé J J, Schwarz S L, Roberts A B, Sporn M B, Rosenberg S A
Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.
Cancer Immunol Immunother. 1988;26(2):95-100. doi: 10.1007/BF00205600.
The effect(s) of purified transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) on the induction and function of lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes (CTL) was examined. The addition of TGF-beta, but not PDGF, to cultures containing fresh C57BL/6 mouse splenocytes or human peripheral blood lymphocytes plus recombinant interleukin-2 markedly inhibited the development of mouse and human LAK cell activity (measured after 3 days for cytotoxicity against cultured or fresh tumor targets in 4-h 51Cr release assays). The addition of TGF-beta, but not PDGF, to a one-way, C57BL/6 anti-DBA/2, mixed lymphocyte reaction effectively blocked the generation of allospecific CTL as well. However, TGF-beta did not inhibit the effector function of LAK cells or of allospecific CTL when added directly to the short-term cytolytic assay. A second form of homodimeric TGF-beta, type 2, was also found to be suppressive on the development of murine LAK cells and allospecific CTL. Collectively, these data demonstrate that the peptide TGF-beta is a potent inhibitor of LAK cell and CTL generation in vitro.
研究了纯化的转化生长因子-β（TGF-β）和血小板衍生生长因子（PDGF）对淋巴因子激活的杀伤细胞（LAK）和细胞毒性T淋巴细胞（CTL）的诱导及功能的影响。在含有新鲜C57BL/6小鼠脾细胞或人外周血淋巴细胞以及重组白细胞介素-2的培养物中添加TGF-β而非PDGF，可显著抑制小鼠和人LAK细胞活性的发展（在4小时51Cr释放试验中，针对培养的或新鲜肿瘤靶标的细胞毒性在3天后测量）。在单向C57BL/6抗DBA/2混合淋巴细胞反应中添加TGF-β而非PDGF，也能有效阻断同种特异性CTL的产生。然而，当直接添加到短期细胞溶解试验中时，TGF-β并不抑制LAK细胞或同种特异性CTL的效应功能。还发现第二种同型二聚体形式的TGF-β，即2型，对小鼠LAK细胞和同种特异性CTL的发展也具有抑制作用。总体而言，这些数据表明肽TGF-β在体外是LAK细胞和CTL生成的有效抑制剂。
