title: Pim1 permits generation and survival of CD4+ T cells in the absence of γc cytokine receptor signaling.
abstract: γ-Chain (γc) cytokine receptor signaling is required for the development of all lymphocytes. Why γc signaling plays such an essential role is not fully understood, but induction of the serine/threonine kinase Pim1 is considered a major downstream event of γc as Pim1 prevents apoptosis and increases metabolic activity. Consequently, we asked whether Pim1 overexpression would suffice to restore lymphocyte development in γc-deficient mice. By analyzing Pim1-transgenic γc-deficient mice (Pim1(Tg) γc(KO) ), we show that Pim1 promoted T-cell development and survival in the absence of γc. Interestingly, such effects were largely limited to CD4(+) lineage αβ T cells as CD4(+) T-cell numbers improved to near normal levels but CD8(+) T cells remained severely lymphopenic. Notably, Pim1 over-expression failed to promote development and survival of any T-lineage cells other than αβ T cells, as we observed complete lack of γδ, NKT, FoxP3(+) T regulatory cells and TCR-β(+) CD8αα IELs in Pim1(Tg) γc(KO) mice. Collectively, these results uncover distinct requirements for γc signaling between CD4(+) αβ T cells and all other T-lineage cells, and they identify Pim1 as a novel effector molecule sufficient to drive CD4(+) αβ T-cell development and survival in the absence of γc cytokine receptor signaling.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Division of Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Linowes
authors.forename: Davinna L
authors.initials: DL
authors.lastname: Ligons
authors.forename: Anna S
authors.initials: AS
authors.lastname: Nam
authors.forename: Changwan
authors.initials: C
authors.lastname: Hong
authors.forename: Hilary R
authors.initials: HR
authors.lastname: Keller
authors.forename: Xuguang
authors.initials: X
authors.lastname: Tai
authors.forename: Megan A
authors.initials: MA
authors.lastname: Luckey
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D019744:Chemokines, C / Q000172:deficiency / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells; D051573:Proto-Oncogene Proteins c-pim-1 / Q000096:biosynthesis / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory
chemical_list: D016827:CD8 Antigens; D019744:Chemokines, C; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018121:Receptors, Cytokine; C496636:Pim1 protein, mouse; D051573:Proto-Oncogene Proteins c-pim-1
keywords: Apoptosis; Cytokines; Homeostasis; Thymopoiesis