Toll-like receptors in cellular subsets of human tonsil T cells: altered expression during recurrent tonsillitis.
BACKGROUND
The palatine tonsils have a pivotal role in immunological detection of airborne and ingested antigens like bacteria and viruses. They have recently been demonstrated to express Toll-like receptors (TLRs), known to recognize molecular structures on such microbes and activate innate immune responses. Their activation might also provide a link between innate and adaptive immunity. In the present study, the expression profile of TLR1-TLR10 was characterized in human tonsil T cells, focusing on differences between subsets of CD4+ T helper (Th) cells and CD8+ cytotoxic T lymphocytes (CTL). The study was also designed to compare the TLR expression in T cells from patients with recurrent tonsillitis and tonsillar hyperplasia.


METHODS
Tonsils were obtained from children undergoing tonsillectomy, and classified according to the clinical diagnoses and the outcome of tonsillar core culture tests. Two groups were defined; recurrently infected tonsils and hyperplastic tonsils that served as controls. Subsets of T cells were isolated using magnetic beads. The expression of TLR transcripts in purified cells was assessed using quantitative real-time RT-PCR. The corresponding protein expression was investigated using flow cytometry and immunohistochemistry.


RESULTS
T cells expressed a broad repertoire of TLRs, in which TLR1, TLR2, TLR5, TLR9 and TLR10 predominated. Also, a differential expression of TLRs in CD4+ and CD8+ T cells was obtained. TLR1 and TLR9 mRNA was expressed to a greater extent in CD4+ cells, whereas expression of TLR3 mRNA and protein and TLR4 protein was higher in CD8+ cells. CD8+ cells from infected tonsils expressed higher levels of TLR2, TLR3 and TLR5 compared to control. In contrast, CD4+ cells exhibited a down-regulated TLR9 as a consequence of infection.


CONCLUSIONS
The present study demonstrates the presence of a broad repertoire of TLRs in T cells, a differential expression in CD4+ and CD8+ cells, along with infection-dependent alterations in TLR expression. Collectively, these results support the idea that TLRs are of importance to adaptive immune cells. It might be that TLRs have a direct role in adaptive immune reactions against infections. Thus, further functional studies of the relevance of TLR stimulation on T cells will be of importance.
Mansson
Anne
A
Laboratory of Clinical and Experimental Allergy Research, Department of Otorhinolaryngology, Malmö University Hospital, Lund University, 205 02 Malmö, Sweden. Anne.Mansson@med.lu.se
Adner
Mikael
M
Cardell
Lars Olaf
LO
D001424:Bacterial Infections; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002648:Child; D002908:Chronic Disease; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D014066:Palatine Tonsil / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014069:Tonsillitis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
D012333:RNA, Messenger; D051193:Toll-Like Receptors