T-cell development and the CD4-CD8 lineage decision

Nat Rev Immunol. 2002 May;2(5):309-22. doi: 10.1038/nri798.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cell Lineage
  • Histocompatibility Antigens / metabolism
  • Membrane Proteins / physiology
  • Models, Immunological*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Notch
  • Signal Transduction
  • Thymus Gland / immunology

Substances

  • Histocompatibility Antigens
  • Membrane Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Notch