Characteristics and genetic control of NK-cell-mediated cytotoxicity activated by naturally acquired infection in the mouse.

Most and perhaps all natural-cell-mediated cytotoxicity (NCMC) may be activated by a response to exogenous infections. Specific-pathogen-free (SPF) mice have little or no natural killer (NK) cell activity, but when they are relocated in conventional conditions, they develop strong NCMC within 2 to 3 days. Unlike other SPF animals, hypothymic nude mice display good NCMC which is further augmented upon their entry into a pathogenic environment. The ontogeny, genetic control and other features of pathogen-activated NCMC resemble those previously described for NK cells. An H2-D region NCMC regulatory gene is active in either a homozygous or heterozygous state, but to be operative seems to require the presence of an additional complementing locus, which maps outside the H-2 complex. It is proposed that H-2 influences NCMC levels by affecting the expression or immunogenicity of NK cell-activating determinants. Recently activated NK cells were non-adherent and lacked Ia and Thy-1 determinants. NCMC was not affected by treatment with monoclonal high-titer Thy-1.2 antisera and complement. However, an Ly-6.2 antiserum did contain anti-NK cytotoxic activity, which was shown by absorption analysis to be distinct from anti-Ly-6.2 activity. The NK antigen has a strain distribution pattern distinct from Ly-5 and other Ly markers, but may be related or identical to NK-1.