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.