Gamma interferon secretion by human Vγ2Vδ2 T cells after stimulation with antibody against the T-cell receptor plus the Toll-like receptor 2 agonist Pam3Cys

Circulating V gamma 2V delta 2 T-cell populations in healthy human beings are poised for rapid responses to bacterial or viral pathogens. We asked whether V gamma 2V delta 2 T cells use the Toll-like receptor (TLR) family to recognize pathogen-associated molecular pattern molecules and to regulate cell functions. Analysis of expanded V gamma 2V delta 2 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 V gamma 2V delta 2 T cells could respond to the TLR2 agonist (S)-(2,3-bis(paimitoyloxy)-(2RS)-propyl)-N-paimitoyl-(R)-Cys-(S)-Ser(S)Lys(4)-OH trihydrochloride (Pam(3)Cys), but the response required coincident stimulation through the gamma delta 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 V gamma 2V delta 2 T-cell responses at the site of infection and promote the rapid development of subsequent acquired antipathogen immunity.