Induction of tumor-specific T lymphocyte responses in vivo by prothymosin alpha.
We have recently reported that administration of ProT alpha 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 alpha [Papanastasiou et al. (1992) Cancer Immunol Immunother 35:145; Baxevanis et al. (1994) Cancer Immunol Immunothera 38:281]. In this report we demonstrated 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 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 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-restricted cytotoxic activities and survived longer. The ProT alpha-induced CD8+ CTL activity was regulated by ProT alpha-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 ProT alpha 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 ProT alpha is capable of inducing nonspecific, as well as tumor-specific CTL responses in vivo. This is of importance since ProT alpha may prove to be useful in clinical protocols aimed at cancer immunotherapy.
Baxevanis
C N
CN
Gritzapis
A D
AD
Spanakos
G
G
Tsitsilonis
O E
OE
Papamichail
M
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002417:Cattle; D002455:Cell Division / Q000502:physiology; D000939:Epitopes; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007939:Leukemia L1210 / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D012515:Mast-Cell Sarcoma / Q000276:immunology / Q000628:therapy; D051379:Mice; D008811:Mice, Inbred DBA; D011498:Protein Precursors / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000939:Epitopes; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin