T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes.
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 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-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.
Juedes
Amy E
AE
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Dr., San Diego, CA 92121, USA.
Rodrigo
Evelyn
E
Togher
Lisa
L
Glimcher
Laurie H
LH
von Herrath
Matthias G
MG
D000818:Animals; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma