Pim1 permits generation and survival of CD4+ T cells in the absence of γc cytokine receptor signaling.
Eur J Immunol
; 43(9): 2283-94, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23712827
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 αß 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 αß T cells, as we observed complete lack of γδ, NKT, FoxP3(+) T regulatory cells and TCR-ß(+) CD8αα IELs in Pim1(Tg) γc(KO) mice. Collectively, these results uncover distinct requirements for γc signaling between CD4(+) αß T cells and all other T-lineage cells, and they identify Pim1 as a novel effector molecule sufficient to drive CD4(+) αß T-cell development and survival in the absence of γc cytokine receptor signaling.
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MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Receptores de Citocinas
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Quimiocinas C
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Proteínas Proto-Oncogênicas c-pim-1
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article