title: Conditional deletion of cytokine receptor chains reveals that IL-7 and IL-15 specify CD8 cytotoxic lineage fate in the thymus.
abstract: The thymus generates T cells with diverse specificities and functions. To assess the contribution of cytokine receptors to the differentiation of T cell subsets in the thymus, we constructed conditional knockout mice in which IL-7Rα or common cytokine receptor γ chain (γ(c)) genes were deleted in thymocytes just before positive selection. We found that γ(c) expression was required to signal the differentiation of MHC class I (MHC-I)-specific thymocytes into CD8(+) cytotoxic lineage T cells and into invariant natural killer T cells but did not signal the differentiation of MHC class II (MHC-II)-specific thymocytes into CD4(+) T cells, even into regulatory Foxp3(+)CD4(+) T cells which require γ(c) signals for survival. Importantly, IL-7 and IL-15 were identified as the cytokines responsible for CD8(+) cytotoxic T cell lineage specification in vivo. Additionally, we found that small numbers of aberrant CD8(+) T cells expressing Runx3d could arise without γ(c) signaling, but these cells were developmentally arrested before expressing cytotoxic lineage genes. Thus, γ(c)-transduced cytokine signals are required for cytotoxic lineage specification in the thymus and for inducing the differentiation of MHC-I-selected thymocytes into functionally mature T cells.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tom M
authors.initials: TM
authors.lastname: McCaughtry
authors.forename: Ruth
authors.initials: R
authors.lastname: Etzensperger
authors.forename: Amala
authors.initials: A
authors.lastname: Alag
authors.forename: Xuguang
authors.initials: X
authors.lastname: Tai
authors.forename: Sema
authors.initials: S
authors.lastname: Kurtulus
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Alex
authors.initials: A
authors.lastname: Grinberg
authors.forename: Paul
authors.initials: P
authors.lastname: Love
authors.forename: Lionel
authors.initials: L
authors.lastname: Feigenbaum
authors.forename: Batu
authors.initials: B
authors.lastname: Erman
authors.forename: Alfred
authors.initials: A
authors.lastname: Singer
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D005434:Flow Cytometry; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism*; D015851:Interleukin-7 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000235:genetics*; D053647:Receptors, Interleukin-15 / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D015851:Interleukin-7; D018121:Receptors, Cytokine; D053647:Receptors, Interleukin-15; D020395:Receptors, Interleukin-7; C576410:interleukin-7, mouse