The Journal of Experimental Medicine
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Published 5 July 2005. doi:10.1084/jem.20050359
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 1, 111-121
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ARTICLE

 The timing of TCR{alpha} expression critically influences T cell development and selection

Troy A. Baldwin, Michelle M. Sandau, Stephen C. Jameson, and Kristin A. Hogquist

Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455

CORRESPONDENCE Kristin A. Hogquist: hogqu001{at}umn.edu

Sequential rearrangement of the T cell receptor for antigen (TCR) ß and {alpha} chains is a hallmark of thymocyte development. This temporal control is lost in TCR transgenics because the {alpha} chain is expressed prematurely at the CD4–CD8– double negative (DN) stage. To test the importance of this, we expressed the HY{alpha} chain at the physiological CD4+CD8+ double positive (DP) stage. The reduced DP and increased DN cellularity typically seen in TCR transgenics was not observed when the {alpha} chain was expressed at the appropriate stage. Surprisingly, antigen-driven selection events were also altered. In male mice, thymocyte deletion now occurred at the single positive or medullary stage. In addition, no expansion of CD8{alpha}{alpha} intestinal intraepithelial lymphocytes (IELs) was observed, despite the fact that HY transgenics have been used to model IEL development. Collectively, these data establish the importance of proper timing of TCR expression in thymic development and selection and emphasize the need to use models that most accurately reflect the physiologic process.

Abbreviations used: CFSE, carboxyfluorescein diacetate succinimidyl ester; DN, double negative; DP, double positive; HP, homeostatic proliferation; IEL, intraepithelial lymphocyte; SP, single positive.


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