Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice.
Following successful gene rearrangement at alphabeta T-cell receptor (TCR) loci, developing thymocytes express both CD4 and CD8 co-receptors and undergo a life-or-death selection event, which is known as positive selection, to identify cells that express TCRs with potentially useful ligand specificities. Positively selected thymocytes must then differentiate into either CD4(+) helper T cells or CD8(+) cytotoxic T cells, a crucial decision known as CD4/CD8-lineage choice. In this Review, we summarize recent advances in our understanding of the cellular and molecular events involved in lineage-fate decision and discuss them in the context of the major models of CD4/CD8-lineage choice.
Singer
Alfred
A
Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA. singera@mail.nih.gov
Adoro
Stanley
S
Park
Jung-Hyun
JH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019070:Cell Lineage; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D011494:Protein Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D011494:Protein Kinases