Immunoglobulins stimulate central nervous system remyelination: Electron microscopic and morphometric analysis of proliferating cells

Infection with the Daniel strain of Theiler's murine encephalomyelitis virus results in immune-mediated primary demyelination in the spinal cords of susceptible SJL/J mice. Treatment of chronically infected mice (3 to 7 months) with purified immunoglobulins directed against spinal cord homogenate resulted in an increase in the number and average size of lesions that were undergoing remyelination by oligodendrocytes. In vivo autoradiography with [³H]thymidine demonstrated labeling of many lymphocytes in areas of demyelination and remyelination. A direct correlation was found between number of labeled lymphocytes infiltrating the lesion and size of demyelinating lesions. Remyelinated areas contained proliferating cells that resembled immature oligodendrocytes or progenitor glial cells morphologically. The number of labeled presumptive glial cells correlated with the area of remyelination. However, central nervous system remyelination occurred even in the presence of proliferating lymphocytes and astrocytic hypertrophy. In addition, treatment of normal uninfected SJL/J mice with antiserum to spinal cord homogenate resulted in increased numbers of proliferating cells in the spinal cord. These experiments suggest that immunoglobulins to a spinal cord antigen may induce proliferation of cells in the central nervous system to promote remyelination.