Potentiation of antitumor CTL response by GM-CSF involves a B7-dependent mechanism.
We have previously demonstrated the importance of endogenous GM-CSF production for the B7-2-dependent potentiating effect of exogenous TNF for CTL generation by stimulation cultures of splenic cells from mice bearing a large MOPC-315 tumor. Here we show that addition of GM-CSF to stimulation cultures of such tumor-bearer splenic cells also leads to the generation of enhanced anti-MOPC-315 CTL activity via a B7-dependent mechanism. However, while the potentiating effect of TNF was previously shown to be IL-2-independent, the potentiating effect of GM-CSF is shown here to be completely IL-2-dependent. Still, the potentiating activity of exogenous GM-CSF for the in vitro generation of CTL activity is shown to depend completely on endogenous TNF production. Finally, TNF and GM-CSF may cooperate in enhancing the in vivo generation of CTL activity in MOPC-315 tumor bearers because low-dose melphalan (L-phenylalanine mustard) therapy, which was previously shown to lead to the rapid up-regulation of TNF production at the tumor site and the subsequent TNF-dependent in vivo acquisition of potent CTL activity, is shown here to lead to the rapid up-regulation of GM-CSF production at the tumor site.
Mokyr
M B
MB
Department of Biochemistry, University of Illinois at Chicago 60680, USA.
Kalinichenko
T V
TV
Gorelik
L
L
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018122:B7-1 Antigen / Q000502:physiology*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007376:Interleukin-2 / Q000502:physiology*; D008558:Melphalan / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008558:Melphalan