Mechanism of preventive immunization with the aid of Rauscher virus culture having an attenuated leukemogenic potential

Abstract

AbstractThe experiments reported here were aimed at elucidating mechanisms involved in the immunization of mice against Rauscher leukemia with the aid of in vitro cultivated cells chronically infected with the “attenuated” Rauscher virus.BALB/c mice were implanted intraperitoneally with Algire‐type, 0.45 μ porosity, Millipore chambers containing Rauscher‐virus‐infected cells. The animals developed leukemia when the cells in the chambers originated from leukemic spleens producing the virulent virus. On the contrary, when the cells in the chambers originated from cultures producing “attenuated” virus, the mice developed no disease but firm and specific immunity.Cytotoxic tests performed with anti‐viral sera, obtained in hyperimmunized mice or monkeys, showed that the density of viral antigen was of the same order of magnitude on the surface of cells infected in vivo with the highly leukemogenic virus (leukemic spleen cells), as on cells infected in vitro and showing a moderately or highly attenuated leukemogenic potential. These data were fairly concordant with the results of electron microscopic examinations of the corresponding cell preparations for the presence of type C and A virus particles, which were equally abundant in both cases.In addition to the neutralization of the virus by circulating anti‐viral antibodies, other mechanisms seem to be operating in animals vaccinated with the in vitro virus cultures. It appears that these animals were protected not only against challenge with the virulent virus but also against inoculation with leukemic cells. On the other hand, immunity produced by this type of vaccination could be efficiently transmitted by transfer of lymphoid cells from immunized donors to intact recipient animals even if these animals had no detectable anti‐viral antibodies when they were challenged with the virulent virus.In conclusion, the mechanism of immunization with the aid of “attenuated” Rauscher virus cultures is of a complex nature. It is conditioned on the one hand by the production of circulating anti‐viral antibodies induced by the in vitro “attenuated” cultured virus, antigenically similar or identical to the “virulent” virus; on the other hand, one has to envisage an immunological mechanism of a cellular type which can be transferred by sensitized lymphoid cells and which may be induced by a cellular neoantigen common to the in vitro infected cell cultures and the leukemic cells.