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The Journal of Immunology, 2006, 176: 4553-4561.
Copyright © 2006 by The American Association of Immunologists

Antigen Challenge Inhibits Thymic Emigration1

Adam P. Uldrich2,*,{dagger}, Stuart P. Berzins*, Mark A. Malin{dagger}, Philippe Bouillet{ddagger}, Andreas Strasser{ddagger}, Mark J. Smyth§, Richard L. Boyd3,{dagger} and Dale I. Godfrey3,*

* Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia; {dagger} Monash Immunology and Stem Cell Laboratories, Science, Technology, Research and Innovation Project, Monash University, Clayton, Victoria, Australia; {ddagger} Walter and Eliza Hall Institute, Parkville, Victoria, Australia; and § Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia

T cell development in the thymus involves a series of TCR-mediated control points including TCR-beta selection and positive and negative selection. Approximately half of the thymic sojourn is spent in the medulla, where thymocytes undergo final maturation before emigrating to the periphery. Although it is acknowledged that thymic emigration is an active process, relatively little is known about how this is regulated, why it takes so long, and whether TCR-mediated signaling can influence this step. Using wild-type and TCR transgenic mice, we found that Ag injected i.v. or intrathymically led to a striking reduction in the number of recent thymic emigrants (RTE) in the periphery. This was caused by inhibition of T cell export rather than peripheral deletion, because a cohort of RTE that was already released before in vivo Ag challenge was not depleted, and similar results were observed in Bim-deficient mice, which have impaired T cell deletion. Within the thymus, the loss of RTE was associated with retention of medullary thymocytes rather than increased negative selection. In addition to Ag-specific inhibition of export, some TCR-independent suppression of emigration was also observed that appeared to be partly the result of the inflammatory cytokine TNF. Thus, in addition to its accepted role in intrathymic selection events, TCR signaling can also play an important role in the regulation of thymic emigration.


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The JI 2006 176: 4507-4508. [Full Text]  



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M. A. Weinreich and K. A. Hogquist
Thymic Emigration: When and How T Cells Leave Home
J. Immunol., August 15, 2008; 181(4): 2265 - 2270.
[Abstract] [Full Text] [PDF]




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