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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900668v1 183/4/2373    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Wu, P.-S. Articles by Yang-Yen, H.-F. PubMed PubMed Citation Articles by Wu, P.-S. Articles by Yang-Yen, H.-F.

Critical Roles of Translationally Controlled Tumor Protein in the Homeostasis and TCR-Mediated Proliferation of Peripheral T Cells¹

Peih-Shan Wu^*,, Chia-Yu Yang^*,, Jeffrey Jong-Young Yen^*,, Chiang-Hung Chou, Sung Ho Chen, Chi-Kuang Leo Wang, Yein-Gei Lai, Nan-Shih Liao^*, and Hsin-Fang Yang-Yen^2,*,

^* Graduate Institute of Life Sciences, National Defense Medical Center; Institute of Molecular Biology and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

Translationally controlled tumor protein (TCTP) is expressed throughout T cell development and prominently induced following T cell activation. However, its function(s) during these processes is unclear. Here, we demonstrated that conditional deletion of TCTP before the β selection checkpoint resulted into a partial block of thymocyte development at the double-negative (DN) 3 stage. Deletion of TCTP in the double-positive (DP) stage did not cause any significant phenotype in the thymus except a slight increase of mature CD8 single-positive (SP) thymocytes. In contrast to the very modest phenotype observed in the thymus, a significant reduction of mature T cells was observed in the peripheral lymphoid organs of these two conditional null TCTP mutant mice. Detailed analysis revealed that the latter phenotype (peripheral T cell lymphopenia) was largely due to a decreased viability of mature TCTP-deficient (TCTP^–/–) T cells. Transgenic expression of the anti-apoptotic protein Bcl-2 rescued the partial block of early thymocyte development, but not peripheral T cell lymphopenia of T-lineage-specific TCTP^–/– mice, suggesting that the signaling networks of TCTP in these two processes are not identical. Last, we demonstrated that TCTP^–/– T cells manifested a significant defect in T cell Ag receptor (TCR)-mediated cell proliferation. Further analysis revealed that such defect was due to a marked delay in the initial cell-cycle entry of TCTP^–/– T cells following TCR stimulation. Together, these results indicate that TCTP plays a very modest role in thymocyte development, but is critical for peripheral T cell maintenance and TCR-mediated cell proliferation.

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¹ This study was supported in part by a major theme project from Academia Sinica (AS-94-TP-B08), and by a Grant NSC 92-3112-B-001-016 from the National Science Council of Taiwan.

² Address correspondence and reprint requests to Dr. Hsin-Fang Yang-Yen, Institute of Molecular Biology, Academia Sinica, 128 Yen-Jiou Yuan Road, Section 2, Taipei 11529, Taiwan. E-mail address: imbyy{at}gate.sinica.edu.tw

³ Abbreviations used in this paper: TCTP, translationally controlled tumor protein; DN, double-negative; DP, double-positive; GEF, guanine nucleotide exchange factor; SP, single-positive.