title: Functional expression of NOD2 in freshly isolated human peripheral blood γδ T cells.
abstract: γδ T cells play an important role in anti-infective immunity. The major subset of human γδ T cells selectively recognizes phosphorylated bacterial metabolites of the isoprenoid biosynthesis pathway, so-called phosphoantigens. The activation of γδ T cells is modulated by functionally expressed innate immune receptors, notably Toll-like receptor 2 and 3. It was also reported that in vitro expanded γδ T cells respond to muramyl dipeptide (MDP), the minimal peptidoglycan motif activating the nucleotide-binding oligomerization domain containing 2 (NOD2) receptor, although it is unknown whether ex vivo isolated human γδ T cells express functional NOD2. Here, we report that freshly isolated, highly purified peripheral blood γδ T cells express NOD2 mRNA and detectable amounts of NOD2 protein. The biologically active MDP L-D isomer but not the inactive D-D isomer augmented the interferon-γ (IFN-γ) secretion in phosphoantigen-stimulated peripheral blood mononuclear cells. Moreover, a moderate but reproducible and statistically significant increase in IFN-γ secretion was also observed when highly purified peripheral blood γδ T cells were activated by T cell receptor cross-linking in the presence of MDP. Taken together, our results indicate that in addition to the T cell receptor and Toll-like receptors, circulating human γδ T cells express NOD2 as a third class of pattern recognition receptor for sensing bacterial products.
authors.affiliation: Institute of Immunology, University of Kiel, Kiel, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Marischen
authors.forename: D
authors.initials: D
authors.lastname: Wesch
authors.forename: H-H
authors.initials: HH
authors.lastname: Oberg
authors.forename: P
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: A
authors.initials: A
authors.lastname: Trad
authors.forename: M
authors.initials: M
authors.lastname: Shomali
authors.forename: J
authors.initials: J
authors.lastname: Grötzinger
authors.forename: O
authors.initials: O
authors.lastname: Janssen
authors.forename: V
authors.initials: V
authors.lastname: Tchikov
authors.forename: S
authors.initials: S
authors.lastname: Schütze
authors.forename: D
authors.initials: D
authors.lastname: Kabelitz
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D051192:Receptors, Pattern Recognition / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051192:Receptors, Pattern Recognition; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma