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CD4-CD8 Lineage Differentiation: Thpok-ing into the Nucleus¹

Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

The mature β T cell population is divided into two main lineages that are defined by the mutually exclusive expression of CD4 and CD8 surface molecules (coreceptors) and that differ in their MHC restriction and function. CD4 T cells are typically MHC-II restricted and helper (or regulatory), whereas CD8 T cells are typically cytotoxic. Several transcription factors are known to control the emergence of CD4 and CD8 lineages, including the zinc finger proteins Thpok and Gata3, which are required for CD4 lineage differentiation, and the Runx factors Runx1 and Runx3, which contribute to CD8 lineage differentiation. This review summarizes recent advances on the function of these transcription factors in lineage differentiation. We also discuss how the "circuitry" connecting these factors could operate to match the expression of the lineage-committing factors Thpok and Runx3, and therefore lineage differentiation, to MHC specificity.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Research work in the authors’ laboratory is supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health.

² Address correspondence and reprint requests to Dr. Rémy Bosselut, Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 3015, 37 Convent Drive, Bethesda, MD 20892-4259. E-mail address: remy{at}helix.nih.gov

³ Abbreviations used in this paper: MHC-I, MHC class I; ChIP, chromatin immunoprecipitation; DP, double positive; MHC-II, MHC class II; SP, single positive.