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Virus and Autoimmunity: Induction of Autoimmune Disease in Mice by Mouse T Lymphotropic Virus (MTLV) Destroying CD4⁺ T Cells¹

Stephen S. Morse^*, Noriko Sakaguchi and Shimon Sakaguchi^2,

^* The Rockefeller University, New York, NY 10021; and Department of Immunopathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

Neonatal infection of the mouse T lymphotropic virus (MTLV), a member of herpes viridae, causes various organ-specific autoimmune diseases, such as autoimmune gastritis, in selected strains of normal mice. The infection selectively depletes CD4⁺ T cells in the thymus and periphery for 2–3 wk from 1 wk after infection. Thymectomy 3 wk after neonatal MTLV infection enhances the autoimmune responses and produces autoimmune diseases at higher incidences and in a wider spectrum of organs than MTLV infection alone. On the other hand, inoculation of peripheral CD4⁺ cells from syngeneic noninfected adult mice prevents the autoimmune development. These autoimmune diseases can be adoptively transferred to syngeneic athymic nude mice by CD4⁺ T cells. The virus is not detected by bioassay in the organs/tissues damaged by the autoimmune responses. Furthermore, similar autoimmune diseases can be induced in normal mice by manipulating the neonatal thymus/T cells (e.g., by neonatal thymectomy) without virus infection. These results taken together indicate that neonatal MTLV infection elicits autoimmune disease by primarily affecting thymocytes/T cells, not self Ags. It may provoke or enhance thymic production of CD4⁺ pathogenic self-reactive T cells by altering the thymic clonal deletion mechanism, or reduce the production of CD4⁺ regulatory T cells controlling self-reactive T cells, or both. The possibility is discussed that other T cell-tropic viruses may cause autoimmunity in humans and animals by affecting the T cell immune system, not the self Ags to be targeted by the autoimmunity.

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