Discussion paper: protective immunity in leukemic mice treated with specific "immunogenic" RNA

Mice were actively immunized against Friend leukemia virus tumorigenesis by vaccination with cell-free homogenates derived from infected splenocytes emulsified in Freund's adjuvant. Adoptive immunity was also achieved by transferring splenocytes from actively immunized donor animals intravenously into syngeneic recipient animals challenged with the virus. Furthermore, RNA-rich extracts derived from spleens of actively immunized donor animals were capable of transferring immunity to FLV leukemia when injected into recipient animals challenged with the virus. The "immune RNA," when incubated with normal splenocytes in vitro, followed by washing, resulted in a cell population that also induced adoptive immunity after transfer to normal animals challenged with virus either before, simultaneously with, or after injection of the treated splenocytes. RNase, but not DNase or other enzymes, inactivated the biologie activity of the protective RNA from immune donors. In addition, isogeneic mouse serum that contained neutralizing antibody to FLV also inhibited the protective effect of the specific RNA; sera from control mice immunized with unrelated antigens failed to neutralize the specific RNA. These results indicate that an RNA extract that contains a virus-associated or -induced antigen is formed in the spleens of actively immunized animals and possesses the ability to either directly induce protective immunity in recipient animals challenged with virus or, indirectly, to convert normal splenocytes in vitro to adoptively confer immunity to similar recipients. Further investigations concerning the mechanism by which such immunogenic RNA functions in vivo and in vitro, as well as the physicochemical nature of the RNA complex, especially that portion associated with the tumor virus-associated antigen, are needed.