Cytotoxic T lymphocytes (CTLs) that have been exposed for several days to high concentrations of IL-2 either in vitro or in vivo become highly granular in nature. Considerable attention has been focused on the possibility that these IL-2 induced granules might contain a cytotoxin that could explain how CTLs kill their target cells. How such a mechanism would fit into CTL killing in general is still controversial. What cannot be questioned, however, is that CTLs do not undergo a degranulation process during target cell killing. The contents of CTL granules have been only crudely analyzed. While it is certain that a number of different serine esterases reside in granules, little else is known. We recently began an extensive search for biologically interesting activities released during CTL degranulation. We have defined three activities functionally, and now propose detailed biological, biochemical and molecular genetic analyses of these activities. The three activities we have defined are: CTL inhibition, which is probably a feedback regulatory mechanism for controlling CTL function; T helper cell inhibitin, which may be involved in CD8+ T cell suppression of helper function; and viral inhibitin, which drastically inhibits the ability of mature viral particles to infect cells. Understanding the biochemical basis of these activities will greatly broaden our understanding of CTL function.
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