17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Stimulation of Human CD4 + T Lymphocytes via TLR3, TLR5 and TLR7/8 Up-Regulates Expression of Costimulatory and Modulates Proliferation

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The cells of innate and adaptive immunity, although activated by different ligands, engage in cross talk to ensure a successful immune outcome. Toll-like receptors (TLRs) are key components of the innate immune system and have the ability to detect microbial infection and trigger host defence responses. Otherwise, human T lymphocytes are able to produce most TLRs. Thus, we analyze the capability of some TLR ligands to modulate the function of highly-purified CD4 + T cells. We found that agents acting via TLRs (poly I:C, a TLR3 ligand; flagellin, a TLR5 ligand; and R848, a TLR7/8 ligand) are able to regulate the expression of costimulatory molecules both on purified antigen presenting cells and on purified T lymphocytes. Moreover, the activation mediated by TLRs determines a kinetic expression of B7-family members such as through an inhibition of T lymphocytes delayed proliferation. These findings suggest a functional role of some invading microorganisms in regulating acquired immunity.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Quantitative expression of toll-like receptor 1-10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides.

          The Toll-like receptor (TLR)9 is critical for the recognition of immunostimulatory CpG motifs but may cooperate with other TLRs. We analyzed TLR1-10 mRNA expression by using quantitative real-time PCR in highly purified subsets of human PBMC and determined the sensitivity of these subsets to CpG oligodeoxynucleotides (ODN). TLR1 and TLR6 were expressed in all cell types examined. TLR10 was highly expressed in B cells and weakly expressed in plasmacytoid dendritic cells (PDC). High expression of TLR2 was characteristic for monocytes. PDC and B cells expressed marked levels of TLR7 and TLR9 and were directly sensitive to CpG ODN. In CpG ODN-stimulated PDC and B cells, TLR9 expression rapidly decreased, as opposed to TLR7, which was up-regulated in PDC and decreased in B cells. In monocytes, NK cells, and T cells, TLR7 was absent. Despite low expression of TLR9, monocytes, NK cells, and T cells did not respond to CpG ODN in the absence of PDC but were activated in the presence of PDC. In conclusion, our studies provide evidence that PDC and B cells, but not monocytes, NK cells, or T cells, are primary targets of CpG ODN in peripheral blood. The characteristic expression pattern of TLR1-10 in cellular subsets of human PBMC is consistent with the concept that TLR9 is essential in the recognition of CpG ODN in PDC and B cells. In addition, selective regulation of TLR7 expression in PDC and B cells by CpG ODN revealed TLR7 as a candidate TLR potentially involved in modulating the recognition of CpG motifs.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Toll-like receptors control activation of adaptive immune responses.

            Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-kappaB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation

              Dendritic cells (DC) migrate into inflamed peripheral tissues where they capture antigens and, following maturation, to lymph nodes where they stimulate T cells. To gain insight into this process we compared chemokine receptor expression in immature and mature DC. Immature DC expressed CCR1, CCR2, CCR5 and CXCR1 and responded to their respective ligands, which are chemokines produced at inflammatory sites. Following stimulation with LPS or TNF-alpha maturing DC expressed high levels of CCR7 mRNA and acquired responsiveness to the CCR7 ligand EBI1 ligand chemokine (ELC), a chemokine produced in lymphoid organs. Maturation also resulted in up-regulation of CXCR4 and down-regulation of CXCR1 mRNA, while CCR1 and CCR5 mRNA were only marginally affected for up to 40 h. However, CCR1 and CCR5 were lost from the cell surface within 3 h, due to receptor down-regulation mediated by chemokines produced by maturing DC. A complete down-regulation of CCR1 and CCR5 mRNA was observed only after stimulation with CD40 ligand of DC induced to mature by LPS treatment. These different patterns of chemokine receptors are consistent with "inflammatory" and "primary response" phases of DC function.
                Bookmark

                Author and article information

                Journal
                Open Microbiol J
                TOMICROJ
                The Open Microbiology Journal
                Bentham Open
                1874-2858
                15 January 2009
                2009
                : 3
                : 1-8
                Affiliations
                [1 ]Department of Experimental Medicine, Section of Human Anatomy, University of Genova, Via De Toni 14, 16132 Genova
                [2 ]Section of Internal Medicine, Department of Clinical and Experimental Medicine, University of Verona, Italy
                [3 ]Polizia di Stato, Italy
                Author notes
                [* ]Address correspondence to this author at the Department of Experimental Medicine, Section of Human Anatomy, University of Genova, Via De Toni 14, 16132 Genova (Italy); Tel: +39-010-3537872; Fax: +39-010-3537885; E-mail: daniele.saverino@ 123456unige.it
                Article
                TOMICROJ-3-1
                10.2174/1874285800903010001
                2656776
                19294011
                73c0cb4f-6d93-4413-a263-3443b560da84
                © Simone et al.; Licensee Bentham Open.

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 28 November 2008
                : 5 December 2008
                : 30 December 2008
                Categories
                Article

                Microbiology & Virology
                b7-family receptors,toll-like receptors.,t lymphocytes
                Microbiology & Virology
                b7-family receptors, toll-like receptors., t lymphocytes

                Comments

                Comment on this article