Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.
CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines.
J Clin Invest. 1998 Sep 15;102(6):1112-24. Unique Identifier : AIDSLINE MED/98411367 Kim JJ; Nottingham LK; Sin JI; Tsai A; Morrison L; Oh J; Dang K; Hu Y; Kazahaya K; Bennett M; Dentchev T; Wilson DM; Chalian AA; Boyer JD; Agadjanyan MG; Weiner DB; Department of Chemical Engineering, University of Pennsylvania,; Philadelphia, PA 19104, USA.
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.
Keywords: JOURNAL ARTICLE Animal AIDS Vaccines/IMMUNOLOGY Chemokines/*BIOSYNTHESIS Chemokines, CXC/BIOSYNTHESIS CD8-Positive T-Lymphocytes/*IMMUNOLOGY Female Fusion Proteins, gag-pol/GENETICS/IMMUNOLOGY HIV-1/IMMUNOLOGY Interleukin-8/BIOSYNTHESIS *Lymphocyte Transformation Macrophage Inflammatory Protein-1/BIOSYNTHESIS Mice Mice, Inbred BALB C Models, Immunological RANTES/BIOSYNTHESIS Support, U.S. Gov't, P.H.S. T-Lymphocytes, Cytotoxic Th1 Cells/IMMUNOLOGY Vaccines, DNA/IMMUNOLOGY 981230
M98C6838
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