Immune mechanisms in leukemia: evaluation of immunocompetent cell populations

Dose-response curves of the cellular immune response of C58/wm mice to syngeneic line Ib malignant lymphoid cells (Ib cells) were computer analyzed by the PROBT subroutine in the IBM Scientific Subroutine Package. An analysis of the relative immunogenicity of various admixtures of x-irradiated (XIb) and viable Ib cells (VIb) after i.p. injection showed that the ratio had to be approximately 100:1 to be immunogenic. Viable Ib cells contained in immunogenic mixtures multiplied in vivo at a logarithmic rate up to 5 or 6 days but were eliminated immunologically by 8 or 9 days. Adoptive cell transfer techniques were used to quantify the protective effect of immune spleen cells (ISC). Essentially a constant dose of ISC (10-6.4) protected mice against a challenge dose of 10-2 to 10-5 VIb cells; more than 10-5 VIb cells were lethal. Two techniques were used to quantify immunity even though mice ultimately died of transplanted leukemia, viz., mean survival time (MST) with a fixed challenge dose of VI b cells, or MST with a fixed time for death. The sensitivity and statistical limitations of these assays are presented. To amplify the sensitivity of assays for adoptive cellular immunity a technique of antigenic stimulation was used, viz., 1 day after x-irradiated mice (600 R) received an i.p. injection of normal or immune spleen, bone marrow or thymic cells they received an i.p. injection of XIb cells containing an admixture of VIb cells. The technique amplified the sensitivity of ISC transfer tests approximately 100-fold and made it possible to detect protective effects of bone marrow and thymic cell populations.