レクチンによる抗ＣＤ３抗体添加ｒＩＬ‐２誘導ＬＡＫ細胞の抗腫よう活性増強についての検討

Abstract

Interleukin-2 (IL-2) with anti-CD 3 antibody can induce large numbers of lymphokine activated killer (CD3LAK) cells. However, CD3LAK cells are less cytotoxicity than LAK cells treated with IL-2 alone. Therefore, enhancement by lectins of the cytotoxicity of activated lymphocytes is regarded as lectin-dependent cellular cytotoxicity (LDCC). We studied the enhancement of cytotoxicity by PHA or PWM against PBMC (peripheral blood mononuclear cell)-CD3LAK cells derived from peripheral blood mononuclear cells from a normal donor as well as PBMC-CD3LAK and TIL (tumor infiltrated lymphocyte)-CD3LAK cells obtained from two patients with tongue cancer (stage II). The treatment with PHA or PWM was given to two groups: one (additional group) was treated with PHA or PWM in the effector phase. Another (pretreatment group) was treated with the lectins, described above, and then excess lectin was washed from the surface of the CD3LAK cells. Cytotoxicity in the above two groups was estimated with a 51Cr release assay for four hours. We found that the NK activity of the PBMC-CD3LAK cells derived from a normal donor was significantly enhanced by PHA or PWM, with the exception of NK activity in the pretreatment group. LAK activity of the above cells was enhanced significantly only by PWM in the additional group. In contrast, LAK activity of PBMC-CD3LAK cells derived from case 2 was significantly enhanced by PWM in both groups. The NK activity of TIL-CD3LAK cells derived from case 1 was enhanced by PHA or PWM, and the LAK activity of these cells was also enhanced significantly by PWM in both groups. The LAK activity of TIL-CD3LAK cells derived from case 2 was enhanced by PWM in both groups. As for cytotoxicity against the autologous tumor, PBMC-CD3LAK cells derived from case 2 were also slightly enhanced by PHA or PWM in both groups, but TIL-CD3LAK cells were enhanced significantly more than the PBMC-CD3LAK cells in all studies. These results suggest differences between PBMC-CD3LAK and TIL-CD3LAK cells in repertoire and in the sugar chain expressed on the tumor cell surface. In addition, PHA or PWM induced high levels of TNF-α in both PBMC-CD3LAK and TIL-CD3LAK cells, but this cytokine did not contribute to enhanced cytotoxicity