Oligoclonal T cells in histiocytic necrotizing lymphadenopathy are associated with TLR9+ plasmacytoid dendritic cells.
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+ 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.
Lin
Chung-Wu
CW
Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
Liu
Ting-Yun
TY
Lin
Cheng-Jung
CJ
Hsu
Su-Ming
SM
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002648:Child; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D020042:Histiocytic Necrotizing Lymphadenitis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors