Tcr Silencing during T Cell Development Depends upon Pre-Tcr-Induced Proliferation

Ferrero, I.; Mancini, S.J.C.; Grosjean, F.; Wilson, A.; Otten, L.; MacDonald, H.R.

The Journal of Immunology 177(9): 6038-6043

2006


DOI: 10.4049/jimmunol.177.9.6038
Accession: 068490405

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Abstract
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.