Modulation of cellular anti-tumour responses by tumour-specific T suppressor lymphocytes

Tumour-specific Ts cells, induced by a protocol which simulates early stages of tumourigenesis in BALB/c mice by the syngeneic plasmacytoma ADJ-PC-5, suppress the generation of specific cytotoxic T lymphocytes (CTL) in a primary in vitro mixed lymphocyte tumour culture (MLTC) of BALB/c spleen cells against ADJ-PC-5. The influence of these Ts cells on the generation of non-specific killer cell activity has now been analysed. The data show that non-specific killer cells generated during in vitro MLTC lyse both ADJ-PC-5 and YAC-1 cells. They are different from tumour-specific CTL as shown by cold target inhibition experiments and on the basis of their different phenotype. The generation of non-specific killer activity during MLTC can be completely suppressed by ADJ-PC-5 specific Ts cells. Activation of non-specific killer cells by recombinant interleukin-2 (r IL2) alone is not influenced by these Ts cells. The in vitro data are best explained by assuming that the target for suppression are ADJ-PC-5 specific T helper cells. Their inactivation will result in depletion of IL2 in the culture, which is required to activate non-specific killer cells. Prevention of activation of specific and non-specific killer cells in vitro by activated tumour-specific Ts cells in the presence of the tumour, suggests that similar mechanisms might operate in vivo and that inactivation of tumour-specific T helper cells might be of central relevance.