Region E1a of highly oncogenic adenovirus 12 in transformed cells protects against NK but not LAK cytolysis

Abstract

The sensitivity of a library of adenovirus-transformed rat cell lines to lysis with highly enriched populations of rat NK cells and LAK cells activated in vitro by culture with recombinant human IL-2 was studied and correlated with the tumorigenic potential of these cell lines. The cell lines studied express the transforming E1 region of highly oncogenic Ad12 or nononcogenic Ad2. Two cell lines express recombinant E1A regions. In one the E1A genes were of Ad12 origin and the E1B region was derived from nononcogenic Ad5. In the other, the E1A region was from Ad5 and the E1B genes from Ad12. All cell lines tested which express the early region E1 of Ad12 are tumorigenic in syngeneic rats. The two cell lines which express only the E1A or the E1B genes of Ad12, and the Ad2-transformed cells did not induce tumors. Transformed cell lines which express the E1A region of nononcogenic Ad2 or Ad5 are efficiently killed by rat NK cells, but cells which express the Ad12 E1A genes are resistant to lysis by NK-enriched cell fractions even at high effector:target ratio; cells containing the Ad12 E1 region are also resistant to IFN-activated NK cells. Although such NK-resistant cells have a uniformly low level of class I MHC antigen, their resistance is not affected by MHC antigen level modulation by rat IFN. Ad12-transformed cells resistant to endogeneous NK cells, however, are efficiently lysed by LAK cells stimulated in vitro by recombinant IL-2. Sensitivity to LAK killing is unaffected by IFN treatment of target cells. These results show that expression of the E1A region of highly oncogenic Ad12 in the transformed cells, which confers resistance to endogeneous NK cells, fails to protect against lysis by LAK cells.