What Happens in the Thymus Does Not Stay in the Thymus: How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function.
MHC-restricted CD4(+) and CD8(+) T cells are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. Although the transcriptional control of CD4(+)-CD8(+) lineage choice in the thymus is now better understood, less was known about what maintains the CD4(+) and CD8(+) lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in postthymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4(+)-CD8(+) lineage commitment in the thymus, is critical for CD4(+) T cell helper functions.
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Melanie S
MS
Vacchio
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 remy@helix.nih.gov.
Rémy
R
Bosselut
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002454:Cell Differentiation; D019070:Cell Lineage; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D051379:Mice; D011323:Primates; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D015704:CD4 Antigens; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497211:Zbtb7b protein, mouse; C484225:ZBTB7B protein, human