Successful therapy of Theiler's virus-induced demyelination (DA strain) with monoclonal anti-Lyt-2 antibody

Abstract

The effects of therapy with mAb to T cell subsets were studied in mice with Theiler's murine encephalomyelitis virus-induced demyelination. mAb GK1.5 (directed at class II-restricted T cells) and mAb 2.43 (directed at class I-restricted T cells) depleted the appropriate subset of T cells in lymph nodes, spleens, and peripheral blood for 6 to 8 wk after a single i.p. injection of 1 mg of purified mAb. Early treatment with mAb GK1.5 (days -1, 0, and +1 relative to virus injection) resulted in death, encephalitis, and increased demyelination in the majority of animals tested. Treatment with mAb 2.43 resulted in less meningeal inflammation and fewer demyelinating lesions in the spinal cord, irrespective of whether the mAb was given early or after demyelinating disease was established (days 15, 16, and 17). Beneficial response to mAb therapy did not correlate with titers of virus isolated from the central nervous system or serum. These results indicate an important role of class II-restricted T cells during early disease in preventing overwhelming encephalitis; class I-restricted T cells may be critical during demyelination.