Inhibition of T-cell mediated cytotoxicity by Novobiocin suggests multiple pathways for both CD4+ and CD8+ cytotoxic T cells.
The effect of the topoisomerase II inhibitor Novobiocin on T-cell mediated cytotoxicity was tested under various assay conditions. When effector cells were class I major histocompatibility complex (MHC)-specific CD8+ cytotoxic T cells (Tc), Novobiocin caused a biphasic pattern of inhibition and the two components of the inhibition could be separated based on Ca2+ requirement. Unseparated populations of class II MHC specific Tc, containing CD4+ and CD8+ effectors gave the same pattern of inhibition. When CD8+ cells were depleted from the latter population of effectors, different patterns of inhibition from those obtained with CD8+ Tc were seen and furthermore the target affected the pattern of inhibition. Overall the results add further support to there being more than one pathway of CD8+ T-cell mediated cytotoxicity and further illustrate differences between CD4+ and CD8+ T-cell mediated cytotoxicity.
Department of Cell and Structural Biology, University of Manchester, U.K.
P J
PJ
Wood
A G
AG
Stansfield
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000502:physiology; D004264:DNA Topoisomerases, Type I / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009675:Novobiocin / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D009675:Novobiocin; D000001:Calcimycin; D004264:DNA Topoisomerases, Type I; D002118:Calcium