In favor of the selective model of positive selection.
The mechanisms of thymocyte commitment towards the CD4+ and CD8+ lineage remain unresolved. Two models--one based on instruction, the other on selection--have previously been proposed. The instructional model has been popularly received based on results of earlier studies. However, our data from MHC class II, class I, and double-deficient mice suggest otherwise. There exists a significant population of CD4+ cells that is intermediate in maturity between CD4+ CD8+ and fully mature CD4+ CD8- thymocytes in class II-deficient animals; an analogous population of CD4-CD8+ cells exists in class I-negative mice. We suggest that a selective model in which two TCR-MHC molecule engagements are required: the first induces a random down-modulation of either CD4 or CD8 and some differentiation; the second, involving the participation of the appropriate coreceptor, permits end-stage differentiation.
Chan
S H
SH
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS et Unité 184 de Biologie Moléculaire de l'INSERM, Institut de Chimie Biologique, Strasbourg, France.
Benoist
C
C
Mathis
D
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D013269:Stochastic Processes; D013950:Thymus Gland / Q000166:cytology