The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4+ T cells.
How CD4-CD8 differentiation is maintained in mature T cells is largely unknown. The present study has examined the role in this process of the zinc finger protein Zbtb7b, a critical factor for the commitment of MHC II-restricted thymocytes to the CD4+ lineage. We showed that Zbtb7b acted in peripheral CD4+ T cells to suppress CD8-lineage gene expression, including that of CD8 and cytotoxic effector genes perforin and Granzyme B, and was important for the proper repression of interferon-gamma (IFN-gamma) during effector differentiation. The inappropriate expression of IFN-gamma by Zbtb7b-deficient CD4+ T cells required the activities of Eomesodermin and Runx transcription factors. Runx activity was needed for Granzyme B expression, indicating that Runx proteins control expression of the cytotoxic program. We conclude that a key function of Zbtb7b in the mature CD4+ T cell compartment is to repress CD8-lineage gene expression.
Wang
Lie
L
Laboratory of Immune Cell Biology, Center for Cancer Research (CCR), NCI, National Institutes of Health, Bethesda, MD 20892, USA.
Wildt
Kathryn F
KF
Castro
Ehydel
E
Xiong
Yumei
Y
Feigenbaum
Lionel
L
Tessarollo
Lino
L
Bosselut
Rémy
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics* / Q000276:immunology; D050677:Core Binding Factor Alpha 3 Subunit / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C493730:Runx3 protein, mouse; C497211:Zbtb7b protein, mouse