In Vivo Expression of Perforin by Cd8+ Lymphocytes during an Acute Viral Infection by Lucy

A pore-forming protein (PFP;t also termed perforin or cytolysin) has previously been identified in the granules of CTL and NK cells (1-4) . In the presence of calcium, isolated PFP/perforin lyses a variety of target cells nonspecifically. The pore formation model for cell killing, taking into account the lytic function of perforin, is attractive in that it provides a unifying concept that explains cytotoxicity mediated by both CTL and NK cells . Since all previous biochemical analyses of perforin have been conducted with CTL and NK cells propagated in long-term cultures in vitro, it is not clear whether perforin is expressed in vivo by lymphocytes actively engaged in cell-mediated killing. Moreover, the reported absence of measurable amounts of perforin in CTL primed in vivo (5-7) has led to the suggestion that expression of perforin is inextricably driven by IL-2 in vitro, raising the question as to whether this mechanism of lymphocyte-mediated killing occurs in vivo. To address this issue, we investigated the expression of perforin in animals undergoing acute viral infections . CTL and NK cells have long been associated with antiviral immunity (8-12), and in some instances have been implicated directly in the development of immunopathologic injury (11-14) . We chose to analyse the murine infection produced by lymphocytic choriomeningitis virus (LCMV), a member of the arenavirus family. During acute infection it produces intense but localized inflammatory changes, like leptomeningitis and choroiditis or hepatitis, with massive accumulation of CTL and NK cells in the diseased tissues (11-14). Using two strains ofLCMV (one primarily causing leptomeningitis and the other primarily hepatitis) andby means ofimmunohistochemical analysis, we show here that perforin is found