Critical roles of translationally controlled tumor protein in the homeostasis and TCR-mediated proliferation of peripheral T cells.
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 beta 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.
Wu
Peih-Shan
PS
Graduate Institute of Life Sciences, National Defense Medical Center, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Yang
Chia-Yu
CY
Yen
Jeffrey Jong-Young
JJ
Chou
Chiang-Hung
CH
Chen
Sung Ho
SH
Wang
Chi-Kuang Leo
CK
Lai
Yein-Gei
YG
Liao
Nan-Shih
NS
Yang-Yen
Hsin-Fang
HF
D000818:Animals; D014408:Biomarkers, Tumor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D008024:Ligands; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1