International Immunology Advance Access originally published online on July 21, 2005
International Immunology 2005 17(8):1093-1102; doi:10.1093/intimm/dxh289
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IL-2 Responsiveness of CD4 and CD8 lymphocytes: further investigations with human IL-2Rß transgenic mice
1 Unité d'Immunogénétique Cellulaire, Département de Médecine Moléculaire, Institut Pasteur, 25-28, rue du Dr. Roux, 75724 Paris Cedex 15, France
2 Present address: Unité de Biologie des Interactions Cellulaires, Institut Pasteur, Paris, France
Correspondence to: J. Thèze; E-mail: jtheze{at}pasteur.fr
Responsiveness to IL-2 varies from one lympho-mononuclear subset to another. NK lymphocytes and monocytes spontaneously respond to IL-2 whereas it is generally accepted that T and B lymphocytes need to be activated to fully acquire this competence. To further investigate this phenomenon, we studied human IL-2Rß (hIL-2Rß) transgenic mice constitutively expressing heterospecific, intermediate-affinity IL-2R (hIL-2Rß/mouse IL-2R
c). We noted that the B lymphocytes and monocytes from spleens of these hIL-2Rß transgenic animals failed to grow when cultured in IL-2-containing medium. Under the same experimental conditions, CD4 lymphocytes survived, again without growth, whereas CD8 lymphocytes and NK cells were able to proliferate and develop potent LAK cytotoxicity. The properties of these CD4 and CD8 lymphocytes were then compared after purification. Both subsets expressed functional IL-2R able to induce global protein phosphorylation and, more precisely, signal transducer and activation of transcription 5 and Erk phosphorylation. Therefore, the differential growth potential of these CD4 and CD8 lymphocytes cannot be explained by the lack of IL-2R-dependent early signaling events. When the entrance of purified CD4 and CD8 lymphocytes into the cell cycle was analyzed, we found that the CD4 lymphocytes were unable to enter the G1 phase in the absence of anti-CD3 stimulation. This correlates with the effect of IL-2 on cyclin-dependent kinase inhibitor p27kip1. In CD4 lymphocytes, IL-2 does not affect p27kip1 expression. But in CD8 lymphocytes, IL-2 down-modulates p27kip1. These results indicate that, aside from IL-2R expression and function, IL-2 responsiveness is also controlled by lineage-specific mechanisms.
Keywords: cellular proliferation, cytokine-cytokine receptors, T lymphocytes, transgenic mice
* These authors contributed equally to this work
Transmitting editor: G. Trinchieri
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