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Age Dependence of Immunologically Induced Central Nervous System Disease in C58 Mice¹

Departments of Microbiology [W. H. M., M. R. T.], Pathology [M. R. A.], and Internal Medicine [R. L. L., C. K.], The University of Michigan School of Medicine, Ann Arbor, Michigan 48104

Normal C58/wm mice rapidly lost their capacity to be immunized to syngeneic transplantable line I_b leukemic cells after mice became 6 months old. An age-dependent central nervous system (CNS) disease that occurred in immunized mice was characterized by a monocytic inflammatory response, some demyelination, destruction of neurons in the cord, and paralysis or death. A neuropathogenic virus could not be detected in CNS tissues or line I_b cell suspensions. Lymphoid cells from sensitized mice (those with CNS disease) induced CNS disease when injected i.p. into normal old (10 to 14 months), but not young (2 to 6 months), C58/wm mice. Peritoneal cells from normal young C58/wm mice, after incubation with serum from sensitized mice, induced CNS disease when injected i.p. into old, but not young, C58/wm mice. Serum from sensitized mice induced CNS disease when injected i.p. into normal old, but not young, C58/wm mice. The CNS disease was not inducible in young or old BALB/wm mice.

Experiments were carried out to test whether the leukemogenic virus indigenous to C58 mice could be implicated in the pathogenesis of the disease. Spleen cells from C58/wm mice with spontaneous leukemia, which were rich in virus particles, did not induce CNS disease when they were used to immunize young or old C58/wm mice. A leukemogenic virus derived from C58/wm mice likewise did not induce CNS disease when it was used to immunize young or old normal C58/wm mice. Purified line I_b cell fractions induced CNS disease in old, but not young, C58/wm mice. The CNS disease induced in mice appeared to result from a serummediated immunological response directed against -type isoantigens presumed to be present in leukemic cells and CNS tissue. A hypothesis is presented to account for the age dependence of the CNS disease and some of the elements of its pathogenesis.

¹ Supported by National Cancer Institute Grant 06639 and National Institute of Allergy and Infectious Diseases Grant 5 TI-AI 4408, NIH, USPHS.

² Supported by American Cancer Society Institutional Grant IN-40F.

Received 11/ 4/69. Accepted 1/26/70.