There are two distinct secretory pathways of CTLs: one is directed into the synaptic gap; the other spills over into the surrounding microenvironment and sustains inflammation [71]. The latter paracrine system is mediated by cytokines. They are a large group of molecules acting on diverse targets on the secreting cell and on other effector cells. Their function is mediated by intracellular signaling, usually through a pathway that includes molecules belonging to the Janus family of cytoplasmic tyrosine kinases and their targets, the signal transducing activators of transcription (STATs). The main cytokine secreted by activated CTLs is interferon-g (IFNg). The efficacy of CD8+ T cells to reject tumors in vivo correlated better with their ability to secrete IFN-g than with their in vitro cytotoxic activity [72]. IFN-g secretion was shown to be essential for tumor regression through its paracrine effect on other participating cells [29].

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