title: Nucleotide-binding and oligomerization domain-like receptors and retinoic acid inducible gene-like receptors in human tonsillar T lymphocytes.
abstract: Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) and retinoic acid-inducible gene (RIG)-like receptors (RLRs) are recently discovered cytosolic pattern-recognition receptors sensing mainly bacterial components and viral RNA, respectively. Their importance in various cells and disorders is becoming better understood, but their role in human tonsil-derived T lymphocytes remains to be elucidated. In this study, we evaluated expression and functional relevance of NLRs and RLRs in human tonsillar CD3(+) T lymphocytes. Immunohistochemistry, real-time RT-PCR and flow cytometry revealed expression of NOD1, NOD2, NALP1, NALP3, NAIP, IPAF, RIG-1, MDA-5 and LGP-2 at mRNA and protein levels. Because of the limited number of ligands (iE-DAP, MDP, Alum, Poly(I:C)/LyoVec), functional evaluation was restricted to NOD1, NOD2, NALP3 and RIG-1/MDA-5, respectively. Stimulation with the agonists alone was not enough to induce activation but upon triggering via CD3 and CD28, a profound induction of proliferation was seen in purified CD3(+) T cells. However, the proliferative response was not further enhanced by the cognate ligands. Nonetheless, in tonsillar mononuclear cells iE-DAP, MDP and Poly(I:C)/LyoVec were found to augment the CD3/CD28-induced proliferation of tonsillar mononuclear cells. Also, iE-DAP and MDP were found to promote secretion of interleukins 2 and 10 as well as to up-regulate CD69. This study demonstrates for the first time a broad range of NLRs and RLRs in human tonsillar T cells and that NOD1, NOD2 and RIG-1/MDA-5 act synergistically with αCD3 and αCD28 to induce proliferation of human T cells. Hence, these results suggest that these receptors have a role in T-cell activation.
authors.affiliation: Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Terese
authors.initials: T
authors.lastname: Petterson
authors.forename: Anne
authors.initials: A
authors.lastname: Månsson
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
authors.forename: Lars O
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology; D049109:Cell Proliferation; D002469:Cell Separation; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis* / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D000072640:Interferon-Induced Helicase, IFIH1; D008213:Lymphocyte Activation / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053474:Nod1 Signaling Adaptor Protein / Q000096:biosynthesis* / Q000276:immunology; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis* / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1