Studies on the mechanism of rat natural cellular cytotoxicity and its inhibition by normal rat serum.

Non-immune rat spleen lymphoid cells exhibit the capacity to lyse normal dermal-derived fibroblast target cells in the presence of foetal bovine calf serum (FCS)-containing medium, using a 51Cr-release assay. The addition of as little as 1% normal rat serum (NRS) inhibits this reaction. The present study seeks to identify the conditions of factors that may induce or inhibit the expression of normal effector cell (NEC)-mediated lysis. Possible cytotoxicity promoting or inhibiting soluble products released from effector or target cells on their own or in combination could not be demonstrated. Also, the independence of NEC activity from stimulatory factors specifically present in FCS-supplemented medium was illustrated using a variety of heterologous serum supplements as well as purified bovine serum albumin (BSA). The effects of pre-incubating spleen cells in medium supplemented with FCS and NRS, and interchanging these sera in the assay system at various times, showed that the cytotoxic capacity of NECs develops from otherwise inactive cells, in a time-dependent way, immediately upon removal from the inhibitory influence of NRS. Identification of NRS inhibitory factor showed that it was a non-dialysable, heat-stable (at 56 degrees for 30 min) macromolecule of approximately 14,000 to 26,000 mol. wt.