DEFECTIVE TH1 AND TH2 CYTOKINE SYNTHESIS IN THE T-T CELL PRESENTATIONMODEL FOR LACK OF CD40 CD40 LIGAND INTERACTION/

In this study, T or NK cell clones used as antigen-presenting cells (T - or NK-APC) were shown to he significantly less efficient than profes sional APC in inducing Th1 and Th2 cytokines by antigen-specific T cel l clones. This phenomenon was not related to a limited engagement of T CR by T-APC, since comparable thresholds of TCR down-regulation were s hown when antigen was presented by either T-APC or professional APC. R ather, the stimulatory T-APC weakness was due to their inability, beca use they are CD40(-), to provide the appropriate co-stimuli to respond er T cells both indirectly via IL-12, and partially via direct CD40L t riggering on T cells. Indeed, the simultaneous addition of IL-12 and r eagents directly engaging CD40L on responder T cells restored T cell c ytokine synthesis when antigen was presented by T-APC. In addition, ei ther IL-12 production or blocking of T cell cytokine synthesis by anti -IL-12 p75 antibodies was evident only when professional APC were used in our antigen-specific system. The down-regulation of cytokine synth esis in the system of T-T cell presentation could represent a novel me chanism of immune regulation, which may intervene to switch off detrim ental Th1- or TM-mediated responses induced by antigen presentation am ong activated T cells infiltrating inflamed tissues.