New perspectives on a developmental dilemma: the kinetic signaling model and the importance of signal duration for the CD4/CD8 lineage decision.
Double-positive thymocytes are short-lived bipotential cells whose developmental fate is determined by the specificity of their TCRs. A relatively small number of double-positive thymocytes undergo positive selection in the thymus and these are signaled to differentiate either into CD4(+) or CD8(+) mature T cells. The mechanism by which double-positive thymocytes determine their appropriate CD4/CD8 fate has been the subject of intense theoretical debate and rigorous experimental analysis. In the last year, 'signal duration' has been offered as a replacement for 'signal strength' as a major determinant of the CD4/CD8 decision, a deceptively minor refinement that requires a major change in our understanding of how signaled double-positive thymocytes differentiate into mature T cells. Indeed, the kinetic signaling model provides a radically new perspective on the mechanism by which the CD4/CD8 lineage decision is made.
Singer
Alfred
A
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. singera@mail.nih.gov
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology*; D007700:Kinetics; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000502:physiology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors; D019076:Transgenes
D008024:Ligands; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; C498709:Pag1 protein, mouse; C408142:Pag1 protein, rat; D010750:Phosphoproteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)