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Positive and Negative Regulation of the IL-27 Receptor during Lymphoid Cell Activation¹

Alejandro V. Villarino^*, Joseph Larkin, III, Christiaan J. M. Saris, Andrew J. Caton, Sophie Lucas, Terence Wong, Frederic J. de Sauvage and Christopher A. Hunter^2,*

^* Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, and Wistar Institute, Philadelphia, PA 19104; Department of Molecular Biology, Genentech, South San Francisco, CA 94080; and Department of Inflammation Research, Amgen, Inc., Thousand Oaks, CA 91320

Previous reports have focused on the ability of IL-27 to promote naive T cell responses but the present study reveals that surface expression of WSX-1, the ligand-specific component of the IL-27R, is low on these cells and that highest levels are found on effector and memory CD4⁺ and CD8⁺ T cells. Accordingly, during infection with Toxoplasma gondii, in vivo T cell activation is associated with enhanced expression of WSX-1, and, in vitro, TCR ligation can induce expression of WSX-1 regardless of the polarizing (Th1/Th2) environment present at the time of priming. However, while these data establish that mitogenic stimulation promotes expression of WSX-1 by T cells, activation of NK cells and NKT cells prompts a reduction in WSX-1 levels during acute toxoplasmosis. Together, with the finding that IL-2 can suppress expression of WSX-1 by activated CD4⁺ T cells, these studies indicate that surface levels of the IL-27R can be regulated by positive and negative signals associated with lymphoid cell activation. Additionally, since high levels of WSX-1 are evident on resting NK cells, resting NKT cells, effector T cells, regulatory T cells, and memory T cells, the current work demonstrates that IL-27 can influence multiple effector cells of innate and adaptive immunity.

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