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Toll‐Like Receptor Expression and Function in Subsets of Human γδ T Lymphocytes
Author(s) -
Pietschmann K.,
Beetz S.,
Welte S.,
Martens I.,
Gruen J.,
Oberg H.H.,
Wesch D.,
Kabelitz D.
Publication year - 2009
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2009.02290.x
Subject(s) - biology , t cell , ccl5 , chemokine , natural killer t cell , interleukin 21 , zap70 , toll like receptor , microbiology and biotechnology , t cell receptor , cxcl16 , il 2 receptor , cytotoxic t cell , antigen presenting cell , immunology , chemokine receptor , immune system , innate immune system , in vitro , biochemistry
Two subsets of human γδ T cells can be identified by T cell receptor (TCR) V gene usage. Vδ2Vγ9 T cells dominate in peripheral blood and recognize microbe‐ or tumour‐derived phosphoantigens. Vδ1 T cells are abundant in mucosal tissue and recognize stress‐induced MHC‐related molecules. Toll‐like receptors (TLRs) are known to co‐stimulate interferon‐γ (IFN‐γ) production in peripheral blood γδ T cells and in Vδ2Vγ9 T cell lines. By microarray analysis, we have identified a range of genes differentially regulated in freshly isolated γδ T cells by TCR versus TCR plus TLR3 stimulation. Furthermore, we have investigated TLR expression in freshly isolated Vδ1 and Vδ2 subsets and cytokine/chemokine production in response to TLR1/2/6, 3 and 5 ligands. TLR1,2,6,7 RNA was abundantly expressed in both subsets, whereas TLR3 RNA was present at low levels, and TLR5 and 8 RNA only marginally in both subsets. Despite abundant RNA expression, TLR1 was rarely detectable by flow cytometry. In contrast, TLR2 and TLR6 proteins were detected in purified Vδ1 and Vδ2 T cells, and TLR3 protein was detected intracellularly in both subsets. TLR1/2/6, 3 and 5 ligands co‐stimulated the IFN‐γ and chemokine secretion in TCR‐activated Vδ1 and Vδ2 subsets, although the levels of IFN‐γ secreted by Vδ1 T cells were much lower than those produced by Vδ2 T cells. Our results reveal comparable expression of TLRs and functional responses to TLR ligands in freshly isolated Vδ1 and Vδ2 T cells and underscore the intrinsically different capacity for IFN‐γ secretion of Vδ1 versus Vδ2 T cells.