title: IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17.
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.
authors.affiliation: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Henry
authors.forename: David A
authors.initials: DA
authors.lastname: Ornelles
authors.forename: Latoya M
authors.initials: LM
authors.lastname: Mitchell
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Brzoza-Lewis
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hiltbold
mesh_terms: D000276:Adjuvants, Immunologic / Q000096:biosynthesis* / Q000502:physiology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000096:biosynthesis* / Q000502:physiology; D054414:Chemokine CCL17 / Q000096:biosynthesis* / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D007371:Interferon-gamma / Q000096:biosynthesis; D053765:Interleukin-12 Subunit p35 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D053759:Interleukin-23 / Q000502:physiology; D008089:Listeria monocytogenes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D054402:Chemokine CCL1; D054414:Chemokine CCL17; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D007371:Interferon-gamma