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International Immunology, Vol. 12, No. 10, 1389-1396, October 2000
© 2000 Japanese Society for Immunology

The Pim-1 kinase stimulates maturation of TCRß-deficient T cell progenitors: implications for the mechanism of Pim-1 action

Isabelle Leduc, Holger Karsunky1, Noëlle Mathieu, Thorsten Schmidt1, Christophe Verthuy, Pierre Ferrier and Tarik Möröy1

Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 9, France
1 Institut für Zellbiologie (Tumorforschung), IFZ, Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany

Correspondence to: P. Ferrier and T. Möröy

We demonstrate that overexpression of Pim-1, a cytoplasmic serine/threonine kinase of poorly defined function, results in the development of substantial numbers of CD4+CD8+ double-positive thymocytes in two independent knock-out mouse models (i.e. the RAG-1-deficient and TCRß gene enhancer-deleted mice) in which production of a functionally rearranged TCRß gene (hence the pre-TCR) is impaired. This activity of Pim-1, however, does not affect signaling through the Ras/Raf/MAP kinase cascade nor signaling which mediates suppression of TCRß gene recombination (i.e. allelic exclusion). While overexpression of Pim-1 positively affects cell cycle progression in selected CD4–CD8– double-negative precursors, it did not affect expression of components of the cell cycle machinery, with the exception of the G1-specific phosphatase Cdc25A upon antigen receptor stimulation. We propose that Pim-1 acts downstream, or in parallel, to pre-TCR-mediated selection as one factor involved in the proliferative expansion of ß-selected pre-T cells.

Keywords: ß selection, cell proliferation, T lymphocytes

The first two authors contributed equally to this work

Transmitting editor: L. Du Pasquier


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