| First Author | Linowes BA | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 9 | Pages | 2283-94 |
| PubMed ID | 23712827 | Mgi Jnum | J:201196 |
| Mgi Id | MGI:5512781 | Doi | 10.1002/eji.201242686 |
| Citation | Linowes BA, et al. (2013) Pim1 permits generation and survival of CD4(+) T cells in the absence of gammac cytokine receptor signaling. Eur J Immunol 43(9):2283-94 |
| abstractText | gamma-chain (gammac) cytokine receptor signaling is required for the development of all lymphocytes. Why gammac 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 gammac as Pim1 prevents apoptosis and increases metabolic activity. Consequently, we asked whether Pim1 overexpression would suffice to restore lymphocyte development in gammac-deficient mice. By analyzing Pim1-transgenic gammac-deficient mice (Pim1(Tg) gammac(KO) ), we show that Pim1 promoted T-cell development and survival in the absence of gammac. Interestingly, such effects were largely limited to CD4(+) lineage alphabeta 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 alphabeta T cells, as we observed complete lack of gammadelta, NKT, FoxP3(+) T regulatory cells and TCR-beta(+) CD8alphaalpha IELs in Pim1(Tg) gammac(KO) mice. Collectively, these results uncover distinct requirements for gammac signaling between CD4(+) alphabeta T cells and all other T-lineage cells, and they identify Pim1 as a novel effector molecule sufficient to drive CD4(+) alphabeta T-cell development and survival in the absence of gammac cytokine receptor signaling. |
