NDLI: IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17.

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IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ornelles, David A. Mitchell, Latoya M. Henry, Curtis J. Brzoza-Lewis, Kristina L. Hiltbold, Elizabeth M.
Description	Country affiliation: United States Author Affiliation: Henry CJ ( Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.)
Abstract	IL-12 family members are an important link between innate and adaptive immunity. IL-12 drives Th1 responses by augmenting IFN-gamma 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-gamma 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-gamma 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-gamma 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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	181
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2008-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adjuvants, Immunologic Biosynthesis Cd8-positive T-lymphocytes Immunology Chemokine Ccl17 Chemokine Ccl1 Dendritic Cells Interleukin-12 Subunit P35 Interleukin-12 Subunit P40 Lymphocyte Activation Physiology Animals Metabolism Microbiology Cell Communication Cells, Cultured Interferon-gamma Deficiency Genetics Interleukin-23 Listeria Monocytogenes Mice Mice, Inbred C57bl Mice, Knockout Mice, Transgenic Up-regulation Comparative Study Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17.