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International Immunology Advance Access published online on April 26, 2006
International Immunology, doi:10.1093/intimm/dxl028
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received February 21, 2006
Accepted March 21, 2006

Article

Constitutive expression of the pre-TCR enables development of mature T cells

Silke Schnell 1, Corinne Démollière 2, Paul van den Berk 1, Joerg Kirberg 3, and Heinz Jacobs 1 *

1 Division of Immunology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
2 Department of Immunology, University of Basel, 4056 Basel, Switzerland
3 Max Planck Institute for Immunobiology, 79108 Freiburg, Germany

* To whom correspondence should be addressed.
Heinz Jacobs, E-mail: h.jacobs{at}nki.nl


  Abstract

Expression and signalling through the pre-TCR and the TCR{alpha}{beta} resemble two critical checkpoints during T cell development. We investigated to which extent a pre-TCR can functionally replace mature TCR{alpha} chains during T cell development. For this purpose, transgenic mice were generated expressing the pre-TCR{alpha} (pT{alpha}) under the transcriptional control of TCR{beta} regulatory elements. We report here on the interesting finding that constitutive pT{alpha} expression allows complete T cell maturation. The pre-TCR complex permits a subset of {beta}-selected thymocytes to mature in the absence of TCR{alpha} into peripheral T cells ({beta}T cells) comprising up to 10% of all lymphocytes. Lymphopenia-driven proliferation of these {beta}T cells is similar to that of conventional {alpha}{beta}T cells. Furthermore, {beta}T cells proliferated and acquired effector function upon stimulation with allogeneic MHC.

Keywords: cell differentiation; pre-TCR; T cell development; thymus; transgenic/knockout mice.
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