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IL-12 Produced by Dendritic Cells Augments CD8⁺ T Cell Activation through the Production of the Chemokines CCL1 and CCL17¹

Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157

IL-12 family members are an important link between innate and adaptive immunity. IL-12 drives Th1 responses by augmenting IFN- production, which is key for clearance of intracellular pathogens. IL-23 promotes the development of IL-17-producing CD4⁺ T cells that participate in the control of extracellular pathogens and the induction of autoimmunity. However, recent studies have shown that these cytokines can modulate lymphocyte migration and cellular interactions. Therefore, we sought to determine the individual roles of IL-12 and IL-23 in naive CD8⁺ T cell activation by addressing their ability to influence IFN- production and cellular interaction dynamics during priming by Listeria monocytogenes-infected dendritic cells (DC). We found that IL-12 was the major cytokine influencing the level of IFN- production by CD8⁺ T cells while IL-23 had little effect on this response. In addition, we observed that IL-12 promoted longer duration conjugation events between CD8⁺ T cells and DC. This enhanced cognate interaction time correlated with increased production of the chemokines CCL1 and CCL17 by WT but not IL-12-deficient DC. Neutralization of both chemokines resulted in reduced interaction time and IFN- production, demonstrating their importance in priming naive CD8⁺ T cells. Our study demonstrates a novel mechanism through which IL-12 augments naive CD8⁺ T cell activation by facilitating chemokine production, thus promoting more stable cognate interactions during priming.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by the National Institutes of Health Research Project Grant Program (R01) Grant AI057770-01A1 (to E.M.H.). Additional support was provided by the National Institutes of Health Predoctoral Fellowship Award for Minority Students (F31) Grant AI73245-01A1 (to C.J.H.).

² Address correspondence and reprint requests to Dr. Elizabeth M. Hiltbold, Department of Microbiology and Immunology, 5109 Gray Building, Wake Forest University School of Medicine, Winston-Salem, NC 27157. E-mail address: bhiltbol{at}wfubmc.edu

³ Abbreviations used in this paper: DC, dendritic cell; Lm, Listeria monocytogenes; WT, wild type; MFI, mean fluorescence intensity; ICS, intracellular cytokine staining.