, Volume 40, Issue 6, pp 410-418

Induction of tumor-specific T lymphocyte responses in vivo by prothymosin α

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Abstract

We have recently reported that administration of Pro Tα to DBA/2 mice 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 α [Papanastasiou et al. (1992) Cancer Immunol Immunother 35:145; Baxevanis et al. (1994) Cancer Immunol Immunother 38:281]. In this report we demonstrate that Pro T α, when administered simultaneously with L1210 tumor cells, is capable of generating in DBA/2 animals tumorspecific CD8+ cytotoxic T lymphocytes (CTL). The Pro T α-induced CD8+ CTL lysed their syngeneic L1210 targets in a major histocompatibility complex (MHC)-restricted fashion since monoclonal antibodies (mAb) against the H-2Kd allelic product could inhibit the cytotoxic response. Mice receiving only Pro T α developed non-MHC-restricted cytotoxic activity (NK, and LAK activities) whereas those receiving Pro T α and L1210 tumor cells developed both MHC-restricted (CTL) and non-MHC-restricted cytotoxic activities and survived longer. The Pro T α-induced CD8+ CTL activity was regulated by Pro T α-induced L1210-specific syngeneic CD4+ cells. This was shown in two different ways: first, CD8+-cell-mediated cytotoxic responses against L1210 targets were associated with L1210-specific and MHC-restricted proliferative responses of syngeneic CD4+ cells and, second, CD4+ cells from mice that had received both Pro T α and L1210 tumor cells could enhance in vitro the otherwise weak, MHC-restricted and L1210-specific cytotoxicity of syngeneic CD8+ cells from mice that had received only L1210 cells. Our data suggest that Pro T α is capable of inducing nonspecific, as well as tumor-specific CTL responses in vivo. This is of importance since Pro T α may prove to be useful in clinical protocols aimed at cancer immunotherapy.

This work was supported by a CEC grant to Dr. M. Papamichail