title: IL-15Rα of radiation-resistant cells is necessary and sufficient for thymic invariant NKT cell survival and functional maturation.
abstract: The development of invariant NKT (iNKT) cells depends on the thymus. After positive selection by CD4(+)CD8(+)CD1d(+) cortical thymocytes, iNKT cells proceed from CD44(low)NK1.1(-) (stage 1) to CD44(high)NK1.1(-) (stage 2), and then to CD44(high)NK1.1(+) (stage 3) cells. The programming of cytokine production occurs along the three differentiation stages, whereas the acquisition of NK receptors occurs at stage 3. Stage 3 thymic iNKT cells are specifically reduced in Il15ra(-/-) mice. The mechanism underlying this homeostatic deficiency and whether the IL-15 system affects other thymic iNKT cell developmental events remain elusive. In this study, we demonstrate that increased cell death contributed to the reduction of stage 3 cells in Il15ra(-/-) mice, as knockout of Bim restored this population. IL-15-dependent upregulation of Bcl-2 in stage 3 cells affected cell survival, as overexpression of hBcl-2 partially restored stage 3 cells in Il15ra(-/-) mice. Moreover, thymic iNKT cells in Il15ra(-/-) mice were impaired in functional maturation, including the acquisition of Ly49 and NKG2 receptors and the programming of cytokine production. Finally, IL-15Rα expressed by radiation-resistant cells is necessary and sufficient to support the survival as well as the examined maturation events of thymic iNKT cells.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
authors.forename: Chin-Ling
authors.initials: CL
authors.lastname: Chang
authors.forename: Yein-Gei
authors.initials: YG
authors.lastname: Lai
authors.forename: Mau-Sheng
authors.initials: MS
authors.lastname: Hou
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Huang
authors.forename: Nan-Shih
authors.initials: NS
authors.lastname: Liao
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology* / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D053720:Interleukin-15 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D011828:Radiation Chimera; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000528:radiation effects
chemical_list: D053720:Interleukin-15 Receptor alpha Subunit