Kimura K, Abe Y, Horiuchi A, Miyake M, Kimura S
Second Department of Surgery, Ehime University School of Medicine, Japan.
Cell Immunol. 1995 Aug;164(1):119-25. doi: 10.1006/cimm.1995.1150.
Human lymphokine-activated killer (LAK) cells cultured with interleukin-2 express membrane-associated lymphotoxin (mLT) on the cell surface. mLT-lacking (mLT-) LAK cells, which are generated by culturing without IL-2 for 24 hr, fully retained natural killer (NK) and LAK activity. However, they partially lost their killing activity against various tumor cells when compared to mLT-expressing (mLT+) LAK cells. An anti-LT but not anti-tumor necrosis factor (TNF) antibody somewhat suppressed the killing activity of mLT+ LAK cells against these tumor cells. However, an anti-LT antibody did not alter NK or LAK activity of mLT+ LAK cells. Anti-CD18 (beta chain of LFA-1) and anti-CD54 (ICAM-1) monoclonal antibodies, by inhibiting LAK cell binding to targets, suppressed the killing activity of mLT+ LAK cells. During the process in the cytotoxic assay, mLT+ but not mLT- LAK cells up-regulated ICAM-1 expression on target tumor cells, the effect of which was marginally inhibited by anti-TNF and anti-IFN-gamma but not by anti-LT antibodies. The up-regulation of ICAM-1 expression elicited by LAK cells on target tumor cells was not simply caused by diffused soluble factors but required membrane contact of LAK and target cells. Paraformaldehyde-fixed mLT+ but not mLT- LAK cells up-regulated ICAM-1 expression on target cells. These findings indicate that mLT+ but not mLT- LAK cells up-regulate ICAM-1 expression on target tumor cells via undetermined membrane factor(s), and this effect appears to be at least partially responsible for the higher killing activity of mLT+ LAK cells than that of those lacking mLT in vitro.
用人白细胞介素-2培养的人淋巴因子激活的杀伤（LAK）细胞在细胞表面表达膜相关淋巴毒素（mLT）。通过在无白细胞介素-2的条件下培养24小时产生的缺乏mLT（mLT-）的LAK细胞，完全保留了自然杀伤（NK）和LAK活性。然而，与表达mLT（mLT+）的LAK细胞相比，它们对各种肿瘤细胞的杀伤活性部分丧失。一种抗LT但不抗肿瘤坏死因子（TNF）的抗体在一定程度上抑制了mLT+ LAK细胞对这些肿瘤细胞的杀伤活性。然而，抗LT抗体并未改变mLT+ LAK细胞的NK或LAK活性。抗CD18（淋巴细胞功能相关抗原-1的β链）和抗CD54（细胞间黏附分子-1）单克隆抗体通过抑制LAK细胞与靶标的结合，抑制了mLT+ LAK细胞的杀伤活性。在细胞毒性试验过程中，mLT+而非mLT- LAK细胞上调了靶肿瘤细胞上ICAM-1的表达，抗TNF和抗干扰素-γ对其作用有一定抑制，但抗LT抗体无此作用。LAK细胞引起的靶肿瘤细胞上ICAM-1表达上调并非简单地由扩散的可溶性因子所致，而是需要LAK细胞与靶细胞的膜接触才能发生。经多聚甲醛固定后的mLT+而非mLT- LAK细胞仍能上调靶细胞上ICAM-1表达.这些发现表明mLT+而非mLT- LAK细胞通过未确定的膜因子上调靶肿瘤细胞上ICAM-1的表达，并且这种作用似乎至少部分地解释了在体外mLT+ LAK细胞比缺乏mLT的LAK细胞具有更高杀伤活性的原因。
