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Eur J Immunol. 2013 Sep;43(9):2283-94. doi: 10.1002/eji.201242686. Epub 2013 Jun 21.

Pim1 permits generation and survival of CD4+ T cells in the absence of γc cytokine receptor signaling.

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  • 1Experimental 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.

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.

Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

KEYWORDS:

Apoptosis; Cytokines; Homeostasis; Thymopoiesis

PMID:
23712827
[PubMed - indexed for MEDLINE]
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