INDUCTION OF TUMOR-SPECIFIC T-LYMPHOCYTE RESPONSES IN-VIVO BY PROTHYMOSIN-ALPHA

We have recently reported that administration of ProT alpha to DBA/2 m ice before the inoculation of syngeneic L1210 leukemic cells prolonged the survival of these animals by (a) inducing tumoricidal peritoneal macrophages, (b) enhancing natural killer (NK) and inducing lymphokine -activated killer (LAK) activities in splenocytes and (c) inducing the production of interleukin-2 and tumor necrosis factor alpha [Papanast asiou et al. (1992) Cancer Immunol Immunother 35:145; Baxevanis et al. (1994) Cancer Immunol Immunother 38:281]. In this report we demonstra te that ProT alpha, when administered simultaneously with L1210 tumor cells, is capable of generating in DBA/2 animals tumor-specific CD8(+) cytotoxic T lymphocytes (CTL). The ProT alpha-induced CD8(+) CTL lyse d their syngeneic L1210 targets in a major histocompatibility complex( MHC)-restricted fashion since monoclonal antibodies (mAb) against the H-2K(d) allelic product could inhibit the cytotoxic response. Mice rec eiving only ProT alpha developed non-MHC-restricted cytotoxic activity (NK, and LAK activities) whereas those receiving ProT alpha and L1210 tumor cells developed both MHC-restricted (CTL) and non-MHC-restricte d cytotoxic activities and survived longer. The ProT alpha-induced CD8 (+) CTL activity was regulated by ProT alpha-induced L1210-specific sy ngeneic CD4(+) cells. This was shown in two different ways: first, CD8 (+)-cell-mediated cytotoxic responses against L1210 targets were assoc iated with L1210-specific and MHC-restricted proliferative