Interferon regulatory factor 8 integrates T-cell receptor and cytokine-signaling pathways and drives effector differentiation of CD8 T cells.
We recently demonstrated that differentiation of cytotoxic T cells requires cooperation between T-cell receptor (TCR)/costimulation and γc-cytokines. Here we demonstrate that the transcription factor IFN regulatory factor 8 (IRF8) is expressed in CD8 T cells by the combination of these two signals. More importantly, depletion of IRF8 in these cells abrogated the differentiation of naive CD8 T cells into effector cells in an experimental graft-vs.-host disease mouse model. We also show that IRF8 seems to not operate upstream of other critical factors such as T-bet and eomesodermin, which have been implicated in effector maturation. Collectively, our work shows that IRF8 integrates the TCR/costimulation and γc-cytokine-signaling pathways and mediates the transition of naive CD8 T cells to effector cells, thus identifying IRF8 as one of the molecular regulators of CD8 T-cell differentiation.
Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fumi
F
Miyagawa
Hong
H
Zhang
Atshushi
A
Terunuma
Keiko
K
Ozato
Yutaka
Y
Tagaya
Stephen I
SI
Katz
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006086:Graft vs Host Disease / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000099185:Interferon Regulatory Factor-8
D016207:Cytokines; D050835:Interferon Regulatory Factors; D011948:Receptors, Antigen, T-Cell; D000099185:Interferon Regulatory Factor-8