Age dependence of immunologically induced central nervous system disease in C58 mice.

Abstract

Normal C58/wm mice rapidly lost their capacity to be immunized to syngeneic transplantable line Ib 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 Ib 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 Ib 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 θ-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.