title: CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.
abstract: The potential roles of CD8(+) T-cell-induced chemokines in the expansion of immune responses were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the alpha-chemokines IL-8 and SDF-1alpha and the beta-chemokines MIP-1alpha, RANTES, and MCP-1 along with DNA immunogens and analyzed the resulting antigen-specific immune responses. In a manner more similar to the traditional immune modulatory role of CD4(+) T cells via the expression of Th1 or Th2 cytokines, CD8(+) T cells appeared to play an important role in immune expansion and effector function by producing chemokines. For instance, IL-8 was a strong inducer of CD4(+) T cells, indicated by strong T helper proliferative responses as well as an enhancement of antibody responses. MIP-1alpha had a dramatic effect on antibody responses and modulated the shift of immune responses to a Th2-type response. RANTES coimmunization enhanced the levels of antigen-specific Th1 and cytotoxic T lymphocyte (CTL) responses. Among the chemokines examined, MCP-1 was the most potent activator of CD8(+) CTL activity. The enhanced CTL results are supported by the increased expression of Th1 cytokines IFN-gamma and TNF-alpha and the reduction of IgG1/IgG2a ratio. Our results support that CD8(+) T cells may expand both humoral and cellular responses in vivo through the elaboration of specific chemokines at the peripheral site of infection during the effector stage of the immune response.
authors.affiliation: Department of Chemical Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: L K
authors.initials: LK
authors.lastname: Nottingham
authors.forename: J I
authors.initials: JI
authors.lastname: Sin
authors.forename: A
authors.initials: A
authors.lastname: Tsai
authors.forename: L
authors.initials: L
authors.lastname: Morrison
authors.forename: J
authors.initials: J
authors.lastname: Oh
authors.forename: K
authors.initials: K
authors.lastname: Dang
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: K
authors.initials: K
authors.lastname: Kazahaya
authors.forename: M
authors.initials: M
authors.lastname: Bennett
authors.forename: T
authors.initials: T
authors.lastname: Dentchev
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: A A
authors.initials: AA
authors.lastname: Chalian
authors.forename: J D
authors.initials: JD
authors.lastname: Boyer
authors.forename: M G
authors.initials: MG
authors.lastname: Agadjanyan
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis; D054377:Chemokine CXCL12; D018925:Chemokines / Q000096:biosynthesis*; D019743:Chemokines, CXC / Q000096:biosynthesis; D005260:Female; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018448:Models, Immunological; D013602:T-Lymphocytes, Cytotoxic; D018417:Th1 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D015685:Fusion Proteins, gag-pol; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D019444:Vaccines, DNA