CD3(+)CD56(+)CD8(+) cells demonstrating a suppressor T cell-like function in the peripheral blood of colon cancer patients

We previously reported that HLA-unrestricted CTLs against MUC-1 were induce d from colon cancer patients by stimulating peripheral blood lymphocytes (P BLs) with recombinant MUC-1 vaccinia virus (rVMUC-1). We have performed ado ptive immunotherapy (AI) for two gastric and two colon cancer patients, usi ng the rVMUC-1-stimulated T lymphocytes. A significant level of HLA-unrestr icted cytotoxicity against MUC-1 was induced in the two colon cancer patien ts (pA and pB) during the first adoptive immunotherapy, but extremely reduc ed during the second Al. During the second stimulation phase, the rate of C D3(+)CD56(+)CD8(+) cells were significantly increased and that of CD3(+)CD5 6(-)CD4(+) cells were significantly decreased in the two colon cancer patie nts as compared to the first Al. CD3(+)CD56(+)CD8(+) and CD3(+)CD56(-)CD4() cells were isolated from the second AI of the colon cancer patient (pB) a nd designated as D856 and D4, respectively. The D4 cells demonstrated a hig h 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-speci fic CTL activity of D4 cells was suppressed in a D856/D4 ratio-dependent ma nner. Further, D856 cells were highly lytic for the D4 cells demonstrating HLA-unrestricted cytotoxicity against MUC-1. It is concluded that the reduc tion in HLA-unrestricted cytotoxicity against MUC-1 during the second Al is attributed to the D856 cells killing MUC-1-specific CTLs (D4). Thus, the C D3(+)CD56(+) CD8(+) cells seem likely to behave as a suppressor T cell.