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Publication : Selective reduction of post-selection CD8 thymocyte proliferation in IL-15Rα deficient mice.

First Author  Chow KP Year  2012
Journal  PLoS One Volume  7
Issue  3 Pages  e33152
PubMed ID  22448237 Mgi Jnum  J:187033
Mgi Id  MGI:5435141 Doi  10.1371/journal.pone.0033152
Citation  Chow KP, et al. (2012) Selective reduction of post-selection CD8 thymocyte proliferation in IL-15Ralpha deficient mice. PLoS One 7(3):e33152
abstractText  Peripheral CD8(+) T cells are defective in both IL-15 and IL-15Ralpha knock-out (KO) mice; however, whether IL-15/IL-15Ralpha deficiency has a similar effect on CD8 single-positive (SP) thymocytes remains unclear. In this study, we investigated whether the absence of IL-15 transpresentation in IL-15Ralpha KO mice results in a defect in thymic CD8 single positive (SP) TCR(hi) thymocytes. Comparison of CD8SP TCR(hi) thymocytes from IL-15Ralpha KO mice with their wild type (WT) counterparts by flow cytometry showed a significant reduction in the percentage of CD69(-) CD8SP TCR(hi) thymocytes, which represent thymic premigrants. In addition, analysis of in vivo 5-bromo-2-deoxyuridine (BrdU) incorporation demonstrated that premigrant expansion of CD8SP TCR(hi) thymocytes was reduced in IL-15Ralpha KO mice. The presence of IL-15 transpresentation-dependent expansion in CD8SP TCR(hi) thymocytes was assessed by culturing total thymocytes in IL-15Ralpha-Fc fusion protein-pre-bound plates that were pre-incubated with IL-15 to mimic IL-15 transpresentation in vitro. The results demonstrated that CD8SP thymocytes selectively outgrew other thymic subsets. The contribution of the newly divided CD8SP thymocytes to the peripheral CD8(+) T cell pool was examined using double labeling with intrathymically injected FITC and intravenously injected BrdU. A marked decrease in FITC(+) BrdU(+) CD8(+) T cells was observed in the IL-15Ralpha KO lymph nodes. Through these experiments, we identified an IL-15 transpresentation-dependent proliferation process selective for the mature CD8SP premigrant subpopulation. Importantly, this process may contribute to the maintenance of the normal peripheral CD8(+) T cell pool.
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