Streptococcus pneumoniae cocultured with fibroblasts enhances both interferon production and cytotoxic activity by lymphocytes

Abstract

Cell-mediated cytotoxicity against normal human fibroblasts was dependent on treatment of the fibroblasts with Streptococcus pneumoniae. Both spontaneous and interferon (IFN)-enhanced lymphocytes killed human foreskin (HFS) or skin muscle cells cocultured with S. pneumoniae five- to eightfold more than control nontreated cells. Based on Percoll gradient centrifugation, the cytotoxic effector cell migrated like a large granular lymphocyte. The human IFN produced from mixtures of HFS cells, lymphocytes, and S. pneumoniae was observed to be both a mixture of IFN-alpha and IFN-gamma and in an amount 500 times greater than that observed with lymphocytes on HFS cells alone, and it was in an amount 12 times greater than when lymphocytes and bacteria were cultured together. A mixture of antibodies to IFN-alpha and -gamma added to cocultures of fibroblasts and bacteria blocked the killing of fibroblast targets by lymphocytes (47 versus 13%). Thus, endogenously produced IFN was essential for the effective killing of the fibroblasts. Treatment of HFS cells with IFN before bacterial treatment protected the HFS cells from lysis by lymphocytes. The observation that normal diploid cells exposed to bacteria can be killed by lymphocytes suggests that natural cytotoxic cells are active at the site of bacterial infection and conceivably play roles in defense or pathogenesis.