title: Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR-induced signaling and cytokine production.
abstract: During the immune response to pathogens and autoantigens, CD8T cells are exposed to numerous inflammatory agents including the cytokine IL-12. Previous studies have focused on how IL-12 regulates T cell functions when present during or after the activation of the T cell receptor (TCR). However, recent studies suggest that prior exposure to IL-12 also alters the TCR responsiveness of murine T cells. Whether similar phenomena occur in human activated CD8T cells and the mechanisms mediating these effects remain unexplored. In this study, we observed that pretreatment of human activated CD8T cells with IL-12 results in increased cytokine mRNA and protein production following subsequent TCR challenge. The potentiation of TCR-mediated cytokine release was transient and required low doses of IL-12 for at least 24h. Mechanistically, prior exposure to IL-12 increased the TCR induced activation of select MAPKs and AKT without altering the activation of more proximal TCR signaling molecules, suggesting that the IL-12 mediated changes in TCR signaling are responsible for the increased production of cytokines. Our data suggest that prior treatment with IL-12 potentiates human CD8T cell responses at sites of infection and inflammation, expanding our understanding of the function of this clinically important cytokine.
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Aldo
authors.initials: A
authors.lastname: Vacaflores
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Samantha N
authors.initials: SN
authors.lastname: Freedman
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Chapman
authors.affiliation: Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, United States; Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, United States; Department of Internal Medicine, Division of Immunology, University of Iowa, Iowa City, IA 52242, United States. Electronic address: jon-houtman@uiowa.edu.
authors.forename: Jon C D
authors.initials: JC
authors.lastname: Houtman
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12
keywords: CD8T cells; Human T cells; IL-12; TCR signaling