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

• Published in: The Journal of immunology (1950) Vol. 174; no. 12; pp. 7684 - 7691
• Main Authors: Villarino, Alejandro V, Larkin, Joseph, III, Saris, Christiaan J. M, Caton, Andrew J, Lucas, Sophie, Wong, Terence, de Sauvage, Frederic J, Hunter, Christopher A
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.06.2005
• Subjects: Animals; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Down-Regulation - immunology; Immunologic Memory - genetics; Interleukin-2 - pharmacology; Interleukins - metabolism; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Receptors, Cytokine - antagonists & inhibitors; Receptors, Cytokine - biosynthesis; Receptors, Cytokine - deficiency; Receptors, Cytokine - genetics; Resting Phase, Cell Cycle - genetics; Resting Phase, Cell Cycle - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Toxoplasma gondii; Toxoplasmosis, Animal - genetics; Toxoplasmosis, Animal - immunology; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.174.12.7684

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.