T-cell development and the CD4-CD8 lineage decision.
Cell-fate decisions are controlled typically by conserved receptors that interact with co-evolved ligands. Therefore, the lineage-specific differentiation of immature CD4+ CD8+ T cells into CD4+ or CD8+ mature T cells is unusual in that it is regulated by clonally expressed, somatically generated T-cell receptors (TCRs) of unpredictable fine specificity. Yet, each mature T cell generally retains expression of the co-receptor molecule (CD4 or CD8) that has an MHC-binding property that matches that of its TCR. Two models were proposed initially to explain this remarkable outcome--'instruction' of lineage choice by initial signalling events or 'selection' after a stochastic fate decision that limits further development to cells with coordinated TCR and co-receptor specificities. Aspects of both models now appear to be correct; mistake-prone instruction of lineage choice precedes a subsequent selection step that filters out most incorrect decisions.
Germain
Ronald N
RN
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1892, USA. rgermain@nih.gov
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D006649:Histocompatibility Antigens / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology; D018448:Models, Immunological; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D051880:Receptors, Notch; D015398:Signal Transduction; D013950:Thymus Gland / Q000276:immunology
D006649:Histocompatibility Antigens; D008565:Membrane Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051880:Receptors, Notch