Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment.
The mechanism of T cell lineage commitment remains controversial; to examine it we deleted the CD4-silencer element in the germ line of a mouse using a combination of gene targeting and Cre/LoxP-mediated recombination. We found that these mice were unable to extinguish CD4 expression either in immature thymocytes or mature CD8+ cytotoxic T cells (CTLs), which resulted in the development of major histocompatibility complex class II-restricted double-positive CTLs in the periphery. This finding strongly supports a stochastic over an instructive mechanism of coreceptor down-regulation.
Leung
R K
RK
Nuffield Department of Clinical Medicine, University of Oxford, Level 7, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Thomson
K
K
Gallimore
A
A
Jones
E
E
Van den Broek
M
M
Sierro
S
S
Alsheikhly
A R
AR
McMichael
A
A
Rahemtulla
A
A
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage; D015536:Down-Regulation; D020868:Gene Silencing; D018390:Gene Targeting; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements; D017384:Sequence Deletion; D013269:Stochastic Processes; D016176:T-Lymphocyte Subsets / Q000145:classification; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II