title: Modulation of γδ T cell responses by TLR ligands.
abstract: Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity of γδ T cells.
authors.affiliation: Institute of Immunology, Christian-Albrechts University Kiel, Arnold-Heller Strasse 3, Haus 17, 24105, Kiel, Germany. wesch@immunologie.uni-kiel.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Wesch
authors.forename: Christian
authors.initials: C
authors.lastname: Peters
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.forename: Kathrin
authors.initials: K
authors.lastname: Pietschmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
mesh_terms: D000818:Animals; D002417:Cattle; D006801:Humans; D008024:Ligands; D055666:Lipopeptides / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D008024:Ligands; D055666:Lipopeptides; C508075:Pam(3)CSK(4) peptide; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051193:Toll-Like Receptors; D011070:Poly I-C