PT  - JOURNAL ARTICLE
AU  - Morse, Stephen S.
AU  - Sakaguchi, Noriko
AU  - Sakaguchi, Shimon
TI  - Virus and Autoimmunity: Induction of Autoimmune Disease in Mice by Mouse T Lymphotropic Virus (MTLV) Destroying CD4<sup>+</sup> T Cells
DP  - 1999 May 01
TA  - The Journal of Immunology
PG  - 5309--5316
VI  - 162
IP  - 9
4099  - http://www.jimmunol.org/content/162/9/5309.short
4100  - http://www.jimmunol.org/content/162/9/5309.full
SO  - J. Immunol.1999 May 01; 162
AB  - 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.