Akagi J, Takai E, Tamori Y, Ogawa M
National Kumamoto South Hospital, 2338 Toyofuku, Matsubase-cho, Kumamoto 869-0593, Japan.
Int J Oncol. 2001 Sep;19(3):561-6. doi: 10.3892/ijo.19.3.561.
We previously reported that HLA-unrestricted CTLs against MUC-1 were induced from colon cancer patients by stimulating peripheral blood lymphocytes (PBLs) with recombinant MUC-1 vaccinia virus (rVMUC-1). We have performed adoptive immunotherapy (AI) for two gastric and two colon cancer patients, using the rVMUC-1-stimulated T lymphocytes. A significant level of HLA-unrestricted cytotoxicity against MUC-1 was induced in the two colon cancer patients (pA and pB) during the first adoptive immunotherapy, but extremely reduced during the second AI. During the second stimulation phase, the rate of CD3+CD56+CD8+ cells were significantly increased and that of CD3+CD56-CD4+ cells were significantly decreased in the two colon cancer patients as compared to the first AI. CD3+CD56+CD8+ and CD3+CD56-CD4+ cells were isolated from the second AI of the colon cancer patient (pB) and designated as D856 and D4, respectively. The D4 cells demonstrated a high level of HLA-unrestricted CTL activity against MUC-1, but D856 cells did not. When D856 cells were mixed with D4 cells at a D856/D4 ratio of 1:3, 1:2, and 1:1 and used as effector cells, the HLA-unrestricted and MUC-1-specific CTL activity of D4 cells was suppressed in a D856/D4 ratio-dependent manner. Further, D856 cells were highly lytic for the D4 cells demonstrating HLA-unrestricted cytotoxicity against MUC-1. It is concluded that the reduction in HLA-unrestricted cytotoxicity against MUC-1 during the second AI is attributed to the D856 cells killing MUC-1-specific CTLs (D4). Thus, the CD3+CD56+ CD8+ cells seem likely to behave as a suppressor T cell.
我们之前报道过，通过用重组MUC-1痘苗病毒（rVMUC-1）刺激外周血淋巴细胞（PBLs），可从结肠癌患者中诱导出针对MUC-1的HLA非限制性细胞毒性T淋巴细胞（CTLs）。我们使用rVMUC-1刺激的T淋巴细胞对两名胃癌患者和两名结肠癌患者进行了过继性免疫治疗（AI）。在首次过继性免疫治疗期间，两名结肠癌患者（pA和pB）诱导出了显著水平的针对MUC-1的HLA非限制性细胞毒性，但在第二次AI期间极度降低。在第二次刺激阶段，与首次AI相比，两名结肠癌患者中CD3+CD56+CD8+细胞的比例显著增加，而CD3+CD56-CD4+细胞的比例显著降低。从结肠癌患者（pB）的第二次AI中分离出CD3+CD56+CD8+和CD3+CD56-CD4+细胞，分别命名为D856和D4。D4细胞表现出高水平的针对MUC-1的HLA非限制性CTL活性，但D856细胞没有。当D856细胞与D4细胞以1:3、1:2和1:1的D856/D4比例混合用作效应细胞时，D4细胞的HLA非限制性和MUC-1特异性CTL活性以D856/D4比例依赖性方式受到抑制。此外，D856细胞对表现出针对MUC-1的HLA非限制性细胞毒性的D4细胞具有高度杀伤性。得出的结论是，第二次AI期间针对MUC-1的HLA非限制性细胞毒性降低归因于D856细胞杀死了MUC-1特异性CTLs（D4）。因此，CD3+CD56+CD8+细胞似乎可能表现为抑制性T细胞。
