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.