Gamma interferon secretion by human Vgamma2Vdelta2 T cells after stimulation with antibody against the T-cell receptor plus the Toll-Like receptor 2 agonist Pam3Cys

Circulating Vgamma2Vdelta2 T-cell populations in healthy human beings are poised for rapid responses to bacterial or viral pathogens. We asked whether Vgamma2Vdelta2 T cells use the Toll-like receptor (TLR) family to recognize pathogen-associated molecular pattern molecules and to regulate cell func...

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Bibliographic Details
Published in:Infection and immunity 2006-08, Vol.74 (8), p.4505-4511
Main Authors: Deetz, Carl O, Hebbeler, Andrew M, Propp, Nadia A, Cairo, Cristiana, Tikhonov, Illia, Pauza, C David
Format: Article
Language:English
Subjects:
Antibodies - immunology
Cell Line
Cells, Cultured
Dipeptides - immunology
Dipeptides - pharmacology
Flow Cytometry
Humans
Interferon-gamma - secretion
Lipoproteins - immunology
Lipoproteins - pharmacology
Lymphocyte Activation
Receptors, Antigen, T-Cell, gamma-delta - immunology
Receptors, Antigen, T-Cell, gamma-delta - metabolism
Signal Transduction
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Toll-Like Receptor 2 - agonists
Toll-Like Receptor 2 - genetics
Toll-Like Receptor 2 - metabolism
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Summary:Circulating Vgamma2Vdelta2 T-cell populations in healthy human beings are poised for rapid responses to bacterial or viral pathogens. We asked whether Vgamma2Vdelta2 T cells use the Toll-like receptor (TLR) family to recognize pathogen-associated molecular pattern molecules and to regulate cell functions. Analysis of expanded Vgamma2Vdelta2 T-cell lines showed the abundant presence of TLR2 mRNA, implying that these receptors are important for cell differentiation or function. However, multiple efforts to detect TLR2 protein on the cell surface or in cytoplasmic compartments gave inconsistent results. Functional assays confirmed that human Vgamma2Vdelta2 T cells could respond to the TLR2 agonist (S)-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys4-OH trihydrochloride (Pam3Cys), but the response required coincident stimulation through the gammadelta T-cell receptor (TCR). Dually stimulated cells produced higher levels of cytoplasmic or cell-free gamma interferon and showed increased expression of the lysosome-associated membrane protein CD107a on the cell surface. A functional TLR2 that requires coincident TCR stimulation may increase the initial potency of Vgamma2Vdelta2 T-cell responses at the site of infection and promote the rapid development of subsequent acquired antipathogen immunity.
ISSN:0019-9567