Selective Reduction of Post-Selection CD8 Thymocyte Proliferation in IL-15Rα Deficient Mice

• Published in: PloS one Vol. 7; no. 3; p. e33152
• Main Authors: Chow, Kai-Ping N., Qiu, Jian-Tai, Lee, Jam-Mou, Hsu, Shuo-Lun, Yang, Shan-Che, Wu, Ning-Ning, Huang, Wei, Wu, Tzong-Shoon
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2012; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Bone marrow; CD69 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Proliferation; Cells, Cultured; Cloning; Cytokines; Cytometry; Fc receptors; Female; Flow Cytometry; Fusion protein; Homeostasis; Immune system; Influenza; Interleukin 15; Interleukin-15 - metabolism; Interleukin-15 Receptor alpha Subunit - physiology; Lymph nodes; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Lymphoma - immunology; Lymphoma - metabolism; Lymphoma - pathology; Male; Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Reduction; Rheumatoid arthritis; Rodents; Senescence; Studies; T cell receptors; Thymocytes; Thymocytes - cytology; Thymocytes - immunology; Thymocytes - metabolism; Thymus; Trends; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033152

Peripheral CD8(+) T cells are defective in both IL-15 and IL-15Rα knock-out (KO) mice; however, whether IL-15/IL-15Rα 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-15Rα KO mice results in a defect in thymic CD8 single positive (SP) TCR(hi) thymocytes. Comparison of CD8SP TCR(hi) thymocytes from IL-15Rα 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-15Rα KO mice. The presence of IL-15 transpresentation-dependent expansion in CD8SP TCR(hi) thymocytes was assessed by culturing total thymocytes in IL-15Rα-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-15Rα 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.