In vivo activation of murine natural killer cell functions by human recombinant DNA interleukin 2.

Intraperitoneal (i.p.) injections of purified human recombinant DNA (rDNA)-interleukin 2 (IL 2) resulted in in vivo activation of local natural killer (NK) cell activities in wild-type and congenitally athymic mice. NK cells were identified by short-term cytotoxicity assays against YAC tumor targets and by cell-surface phenotyping. The magnitude of the cytolytic responses was dependent on the IL 2 dose (greater than or equal to 0.1 microgram per injection) and the time period of treatment (the maximum response was on days 3 to 4 after daily treatment). In vivo application of antisera against the murine NK marker asialo GM1 (asGM1) and against interferon-alpha/beta and -gamma (IFN) significantly inhibited NK cell activation. Limiting dilution analysis revealed high frequencies (up to 1 in 1.8 X 10(3)) of in vitro IL 2 reactive mononuclear cells among the peritoneal exudate cells (PEC) of normal mice. rDNA-IL 2 activated non-adherent PEC to proliferate. The majority of these cultures also displayed cytotoxicity against YAC targets. No exogenous IFN was required for either response. Endogenous IFN production did not appear to play an important role for induction of cytotoxicity in this system either. Only a minority of cultures produced measurable levels of IFN without showing excessive cytotoxic activity. In vivo IL 2 treatment resulted in a rapid increase of the total numbers and frequencies of the IL 2 reactive PEC. Hence, IL 2 alone was apparently sufficient for in vitro activation of NK-like activities, whereas IFN-induction by IL 2 was required for in vivo elicitation of similar responses in perhaps the same cell populations.