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¹ Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
² Department of Immunology and Infectious Disease, Harvard School of Public Health and Department of Medicine, Harvard Medical School, Boston, MA 02115

Address correspondence to Matthias G. von Herrath, Div. of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121. Phone: (858) 558-3571; Fax: (858) 558-3579; email: matthias{at}liai.org

The T-box transcription factor T-bet is known to control lineage commitment and interferon- production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter–lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-, but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.

Key Words: autoimmunity • T cell memory • cytokines • lymphocytic choriomeningitis virus • transcription factors

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