title: Selective reduction of post-selection CD8 thymocyte proliferation in IL-15Rα deficient mice.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Kai-Ping N
authors.initials: KP
authors.lastname: Chow
authors.forename: Jian-Tai
authors.initials: JT
authors.lastname: Qiu
authors.forename: Jam-Mou
authors.initials: JM
authors.lastname: Lee
authors.forename: Shuo-Lun
authors.initials: SL
authors.lastname: Hsu
authors.forename: Shan-Che
authors.initials: SC
authors.lastname: Yang
authors.forename: Ning-Ning
authors.initials: NN
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Tzong-Shoon
authors.initials: TS
authors.lastname: Wu
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000378:metabolism*; D053720:Interleukin-15 Receptor alpha Subunit / Q000502:physiology*; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit