The Zinc Finger Transcription Factor Zbtb7b Represses CD8-Lineage Gene Expression in Peripheral CD4 + T Cells

• Published in: Immunity (Cambridge, Mass.) Vol. 29; no. 6; pp. 876 - 887
• Main Authors: Wang, Lie, Wildt, Kathryn F., Castro, Ehydel, Xiong, Yumei, Feigenbaum, Lionel, Tessarollo, Lino, Bosselut, Rémy
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.12.2008; Elsevier Limited
• Subjects: Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell culture; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell division; Cell Lineage - genetics; Cell Lineage - immunology; CELLIMMUNO; Core Binding Factor Alpha 3 Subunit - immunology; Core Binding Factor Alpha 3 Subunit - metabolism; Cytotoxicity; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; Flow cytometry; Gene expression; Gene Expression Regulation - immunology; Lymphocytes; Medical research; Mice; Mice, Knockout; Mice, Transgenic; MOLLIMMUNO; Peptides; Protein expression; Proteins; Rodents; Transcription factors; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - immunology; Transcription Factors - metabolism; MOLLIMMUNO; CELLIMMUNO
• DOI: 10.1016/j.immuni.2008.09.019
• ISSN: 1074-7613

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-γ (IFN-γ) during effector differentiation. The inappropriate expression of IFN-γ 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.