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Immature CD4⁺CD8⁺ Thymocytes and Mature T Cells Regulate Nur77 Distinctly in Response to TCR Stimulation¹

Department of Biology, Haverford College, Haverford, PA 19041

The orphan steroid receptor, Nur77, is thought to be a central participant in events leading to TCR-mediated clonal deletion of immature thymocytes. Interestingly, although both immature and mature murine T cell populations rapidly up-regulate Nur77 after TCR stimulation, immature CD4⁺CD8⁺ thymocytes respond by undergoing apoptosis, whereas their mature descendants respond by dividing. To understand these developmental differences in susceptibility to the proapoptotic potential of Nur77, we compared its regulation and compartmentalization and show that mature, but not immature, T cells hyperphosphorylate Nur77 in response to TCR signals. Nur77 resides in the nucleus of immature CD4⁺CD8⁺ thymocytes throughout the course of its expression and is not found in either the organellar or cytoplasmic fractions. However, hyperphosphorylation of Nur77 in mature T cells, which is mediated by both the MAPK and PI3K/Akt pathways, shifts its localization from the nucleus to the cytoplasm. The failure of immature CD4⁺CD8⁺ thymocytes to hyperphosphorylate Nur77 in response to TCR stimulation may be due in part to decreased Akt activity at this developmental stage.

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 National Science Foundation Grant 0343479. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

² N.C., S.A., C.F., and M.S. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Jennifer A. Punt, Haverford College, 370 Lancaster Avenue, Haverford, PA 19041. E-mail address: jpunt{at}haverford.edu

⁴ Abbreviations used in this paper: DP, double positive; SP, single positive; RT, room temperature; GSK-3, glycogen synthase kinase-3.

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