Perforin and Serine Esterase

Several products of CTL and NK cells, including a pore-forming protein (PFP;t perforin or cytolysin) (1-4) and several serine esterases (SE) (5-12), have been cloned and sequenced . These proteins are localized to cytoplasmic granules and represent the known structural components ofthe pore-formation and granule exocytosis models for cell-mediated killing (13-17). Granule mediators are expressed by CTL and NK cell lines maintained with IL-2, but there is still little information on primary effector lymphocyte populations. Moreover, to date, most ofthe studies have been performed in the murine system . Here, using cDNA probes encoding two SE (SE 1/granzyme A/Hanukah Factor and SE 2/granzyme B) and the recently cloned perforin cDNA, we have initiated studies aimed at understanding how the production of these proteins is regulated in human primary T lymphocytes. We have examined RNA accumulation in response to a number of well-known T cell mitogens and have determined the effect of Cyclosporin A (CsA) on this inducible response.