Oligoclonal T cells in histiocytic necrotizing lymphadenopathy are associated with TLR9+ plasmacytoid dendritic cells

Abstract

Histiocytic necrotizing lymphadenopathy (HNL), a disease of unknown cause, is characterized pathologically by the presence of plasmacytoid dendritic cells (pDCs), which are frequently mixed with oligoclonal T cells (OTCs) and myeloid cells. Toll-like receptors (TLRs 1-10) are a family of pattern recognition receptors of DCs. To investigate the interactions between pDCs and T cells, and to look for an etiology of HNL, we studied 24 HNLs for the profile of TLRs. Transcripts of TLR7, a receptor on pDCs for single-stranded RNA, were found in every case, confirming the universal presence of pDCs. Transcripts of TLR9, another receptor on pDCs for microbial unmethylated CpG-rich DNA, were correlated with OTCs, implying T-cell expansion stimulated by TLR9 þ pDCs in response to a microbe. Because PCRs for bacterial 16S rDNAs were negative in the lymph nodes, a bacterial origin seems unlikely, but a virus remains a possible candidate. The pDCs lacked the maturation marker CD83, which suggested ineffective stimulation of T cells and might account for the usually benign course of HNL. Taken together, these data illustrate a novel approach, based upon TLR transcript analysis, for the integration of pathology, immunology, and clinical findings of HNL.

Different T‐bet expression patterns characterize particular reactive lymphoid tissue lesions

“…Finally, our results support the hypothesis that Kikuchi lymphadenitis is caused by an intracellular microorganism. In a recent investigation of this disease it has been proposed that TLR9 is elevated in plasmacytoid dendritic cells 34 . However, the list of candidates which might cause Kikuchi lymphadenitis is long.…”

“…In a recent investigation of this disease it has been proposed that TLR9 is elevated in plasmacytoid dendritic cells. 34 However, the list of candidates which might cause Kikuchi lymphadenitis is long. In this context, the reported activation of TLR9 by malaria pigment haemozoin 35 as well as the detection of Bartonella henselae gene sequences in lymph nodes of children with Kikuchi disease 36 are of interest because they point out that not only a virus but also parasites remain possible candidates for the cause of this necrotizing lymphadenitis.…”

Immunohistochemical Discrimination of Plasmacytoid Dendritic Cells from Myeloid Dendritic Cells in Human Pathological Tissues

“…15,16 KL is a rare, benign and selflimiting disorder that characteristically presents with fever and cervical lymphadenopathy. 15 Numerous pDC-precursors are present in the T-cell area around the granuloma, 15,16 suggesting that a large number of pDCs are present in KL. Consistently, almost all DCs detected in KL were S100B -/ fascin + DCs, while S100B + DCs were scarcely detected.…”

“…15,16 Thus, mDCs and pDCs are largely different from each other in origin, in function, and in distribution, but no method has been available to distinguish these two subsets immunohistochemically.…”

Increased Expression of CD169 on Monocytes in Adult-Onset Kikuchi–Fujimoto Disease

“…Hemato 2023, 4 274 While KFD is primarily supposed to reflect an aberrant cytotoxic-T-cell-mediated immune response to a variety of antigenic stimuli [8][9][10], the activation of the phagocyte mononuclear cell system has been proposed as a contributory mechanism. First, pathological investigations identified clusters of INFα-producing pDCs as specific histology-based diagnostic markers of KFD [8,11,12].…”