T-bet Controls Autoaggressive CD8 Lymphocyte Responses in Type 1 Diabetes
Open Access
- 19 April 2004
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 199 (8), 1153-1162
- https://doi.org/10.1084/jem.20031873
Abstract
The T-box transcription factor T-bet is known to control lineage commitment and interferon-γ 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-γ, 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.Keywords
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