Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 199, Issue 8, Pages 1153-1162Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20031873
Keywords
autoimmunity; T cell memory; cytokines; lymphocytic choriomeningitis virus; transcription factors
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Funding
- NIAID NIH HHS [R01 AI044451, AI44451, U19 AI51973, U19 AI051973] Funding Source: Medline
- NIDDK NIH HHS [R29 DK051091, DK51091, R01 DK051091] Funding Source: Medline
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The T-box transcription factor T-bet is known to control lineage commitment and interferon-gamma production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of ON lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter lymphocytic choriomeningitis virus (LCMV) transgenic model for Z, virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-gamma, 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.
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