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Immune Mechanisms in Leukemia: Evaluation of Immunocompetent Cell Populations¹

From the Department of Microbiology, The University of Michigan, School of Medicine, Ann Arbor, Michigan 48104

Abstract

Dose-response curves of the cellular immune response of C58/wm mice to syngeneic line I_b malignant lymphoid cells (I_b 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 (XI_b) and viable I_b cells (VI_b) after i.p. injection showed that the ratio had to be approximately 100:1 to be immunogenic. Viable I_b 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 10² to 10⁵ VI_b cells; more than 10⁵ VI_b 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 XI_b cells containing an admixture of VI_b 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.

Footnotes

¹ This work was supported by Grant CA13701 from the National Cancer Institute, United States Public Health Service.