Cytotoxic cell proteinase gene expression and cytolytic activity by anti-CD3-activated cytotoxic T lymphocytes is sensitive to cyclosporin A but is not dependent on interleukin-2 synthesis.
We have examined the role of interleukin (IL) 2 in the expression of cytotoxic cell proteinases (CCP) 1 and 2, as well as in the induction of major histocompatibility complex (MHC)-unrestricted cytotoxic activity in murine T cell cultures following stimulation with anti-CD3 monoclonal antibody. A dramatic reduction in CCP-1 and CCP-2 gene expression and near absence of cytolytic activity was shown to occur in these cultures when the expression of IL-2 was inhibited by 10(-6) M cyclosporin A (CsA). The inhibitory effect of CsA could not be eliminated by the addition to culture of recombinant IL-2 at concentrations typically present in anti-CD3-stimulated T cell culture supernatants. Furthermore, when endogenous IL-2 (45-60 U/ml) present in anti-CD3-stimulated T cell cultures was neutralized with anti-mouse IL-2 antibody there was no effect on CCP-1 and CCP-2 mRNA expression and only a slight decrease in cytolytic activity. The expression of CCP-1 and CCP-2 gene products and the induction of MHC-unrestricted cytotoxic activity in anti-CD3-stimulated T cell cultures therefore occur independently of IL-2 synthesis but are regulated by a CsA-sensitive mechanism.
Kaiser
M
M
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Brooks-Kaiser
J
J
Fitzpatrick
L
L
Bleackley
R C
RC
Hoskin
D W
DW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015152:Blotting, Northern; D017252:CD3 Complex / Q000276:immunology*; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D012515:Mast-Cell Sarcoma; D051379:Mice; D008808:Mice, Inbred CBA; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D012333:RNA, Messenger; D016572:Cyclosporine; D012697:Serine Endopeptidases; C057818:cytotoxic T lymphocyte-specific serine protease