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The Journal of Immunology, 2009, 182, 4581 -4589
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0900010

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Thymic OX40 Expression Discriminates Cells Undergoing Strong Responses to Selection Ligands 1

Mark Klinger2,*, Joong Kyu Kim2,*, Stephen A. Chmura*, Andrea Barczak{dagger}, David J. Erle{dagger} and Nigel Killeen3,*

* Department of Microbiology and Immunology and {dagger} Lung Biology Center, Department of Medicine, University of California, San Francisco, CA 94143

OX40 is a member of the TNF receptor family expressed on activated and regulatory T (Treg) cells. Using an Ox40-cre allele for lineage marking, we found that a subpopulation of naive T cells had also previously expressed OX40 in the thymus. Ox40-cre was induced in a small fraction of thymocytes that were OX40+, some of which were CD25high Treg cell precursors. Thymic OX40 expression distinguished cells experiencing a strong signaling response to positive selection. Naive T cells that had previously expressed OX40 demonstrated a partially activated phenotype that was distinct from that of most naive T cells. The results are consistent with the selection of Treg cells and a minor subpopulation of naive T cells being dependent on strong signaling responses to thymic self ligands.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Grant AI39506 from the National Institutes of Health. N.K. was supported by a Scholar Award from the Leukemia and Lymphoma Society, and M.K. was supported by a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship award.

2 M.K. and J.K.K. contributed equally to this paper.

3 Address correspondence and reprint requests to Dr. Nigel Killeen, Department of Microbiology and Immunology, University of California at San Francisco, 513 Parnassus Avenue, Room HSE 1001, San Francisco, CA 94143. E-mail address: nigel.killeen{at}ucsf.edu

4 Abbreviations used in this paper: Treg, regulatory T; IRES, internal ribosomal entry site; TREC, TCR rearrangement excision circle.

5 The online version of this article contains supplemental material.







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