Increased responses to lymphokines are correlated with preleukemia in mice inoculated with Moloney leukemia virus

In various mouse strains, inoculation with Moloney leukemia virus results in the establishment of an acute viremia which in most cases is followed by the induction of leukemia. Also associated with the viremia is the development of a chronic cellular immune response detectable in vitro by the ability of viral proteins to induce splenic lymphocyte proliferation. Previous studies have demonstrated that, in the absence of this cellular immune response, leukemia does not develop irrespective of whether viremia is present [Lee, J. C. & Ihle, J. N. (1981) Nature (London) 289, 407-409]. In vitro proliferative responses to antigens involve the nonspecific response of various subpopulations of lymphocytes to lymphokines produced by antigen-specific Thy 1+, Lyt 1+,2- lymphocytes. The studies presented here concern the effects of a chronic immune response in viremic mice on the frequency of lymphocytes capable of responding to lymphokines in vitro. The data demonstrate that the number of responsive lymphocytes is increased 30- to 100-fold in preleukemic mice and that such increases are dependent upon the induction of an immune response in viremic mice. The role of this altered immune response in leukemia is discussed.