TCRgamma silencing during alphabeta T cell development depends upon pre-TCR-induced proliferation.
During thymus development, immature T cells become committed to two distinct lineages based upon expression of alphabeta or gammadelta TCR. In the alphabeta lineage, developing thymocytes progressively extinguish transcription of the TCRgamma genes by a poorly understood process known as gamma silencing. We show that alphabeta lineage thymocytes in mice lacking a functional pre-TCR undergo limited proliferation and fail to silence TCRgamma genes during development. Stimulation of pre-TCR-deficient immature thymocytes with anti-CD3 Abs does not directly down-regulate TCRgamma transcription but restores TCRgamma silencing following proliferation. Collectively our data reveal an important role for pre-TCR induced proliferation in activating the TCRgamma silencer in alphabeta lineage thymocytes, a process that may reinforce alphabeta or gammadelta lineage commitment.
Ferrero
Isabel
I
Ludwig Institute for Cancer Research-Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland.
Mancini
Stéphane J C
SJ
Grosjean
Frederic
F
Wilson
Anne
A
Otten
Luc
L
MacDonald
H Robson
HR
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D020868:Gene Silencing; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000819:agonists / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000819:agonists / Q000235:genetics*; D037941:Silencer Elements, Transcriptional / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology
D000906:Antibodies; D017252:CD3 Complex; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta