Effects of Antilymphocyte Serum (ALS) on the Induction of Lymphocytic Leukemia in Mice

Discussion and summary

The immune deficit created in 12-week-old BALB/c mice by as small a dose of ALS as 0.2 ml, in divided doses, is sufficient to provide susceptibility to the leukemogenic effects of MLV. ALS alone at various dosage levels was found not to be leukemogenic.

The immunosuppressive effect of ALS in all probability allows the survival of cells converted to neoplasia by virus; these cells are so highly antigenic that they would be eliminated in the normal animal. MLV is known to induce resistance against the transplantation of lymphoma cells carrying the corresponding antigen in BALB/c mice. Thus, as with DNA virus-induced neoplasms immune suppression and tumor antigens of the transplantation type appear to be major determinants in tumor induction with an RNA virus, MLV. That this is so is shown by the lack of increased susceptibility in those animals rendered tolerant at birth to virus or to new virus-specified cellular antigens (14). In this situation immunosuppression as observed is expected to have a negligible influence.

The reversal of susceptibility in ALS-treated BALB/c mice by adoptive transfer of syngeneic adult normal lymphoid cells probably represents replacement of those immune elements removed by ALS. Critical factors in the reversal were both timing and size of the adoptive transfer cells. The increased frequency and lowered latent period of ALS-treated recipients of “sensitized” lymphoid cells probably represents immunologic enhancement but this remains to be determined.

ALS appears to remove selectively or inactivate those cells concerned with the establishment and maintenance of immunocompetence but to be relatively ineffective against cells of lymphoid origin susceptible to transformation by MLV from the normal to the neoplastic state.

ALS administration prior to infection with leukemogenic virus inhibited antiviral antibody but provided leukemia induction, whereas ALS administered after MLV was largely ineffective. This most likely signified that a major effect of ALS is upon antigen-sensitive cells [see (21)]. The precise role of antiviral antibody, however, has not been determined.

The model systems described lend themselves to studies of the mechanisms concerned with susceptibility and resistance to lymphoid neoplasms induced in the primary host.