Cutting edge: T-bet and IL-27R are critical for in vivo IFN-gamma production by CD8 T cells during infection.
CD8+ T cells are a major source of IFN-gamma, a key effector cytokine in immune responses against many viruses and protozoa. Although the transcription factor T-bet is required for IFN-gamma expression in CD4+ T cells, it is reportedly dispensable in CD8+ T cells, where the transcription factor Eomesodermin is thought to be sufficient. The diverse functions of IFN-gamma are mediated through the IFN-gammaR and STAT1. In CD4+ T cells, STAT1 appears to be critical for the activation of T-bet and IFN-gamma, suggesting an IFN-gamma-dependent positive feedback loop. However, STAT1 can also be activated by other cytokines, including IL-27. In the present study we show that, in contrast to in vitro conditions and the prevailing paradigm, T-bet is critical for the in vivo IFN-gamma production by CD8+ T cells upon infection of mice with diverse pathogens. Whereas IFN-gammaR signals are dispensable for the T-bet-dependent IFN-gamma production, direct IL-27Ralpha signals are critical.
Mayer
Katrin D
KD
Trudeau Institute, Saranac Lake, NY 12983, USA.
Mohrs
Katja
K
Reiley
William
W
Wittmer
Susan
S
Kohlmeier
Jacob E
JE
Pearl
John E
JE
Cooper
Andrea M
AM
Johnson
Lawrence L
LL
Woodland
David L
DL
Mohrs
Markus
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007239:Infections / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D007251:Influenza, Human / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000502:physiology*; D014123:Toxoplasmosis / Q000276:immunology; D000098815:T-bet Transcription Factor
C484747:Il27ra protein, mouse; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma