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Gamma Interferon Secretion by Human V2V2 T Cells after Stimulation with Antibody against the T-Cell Receptor plus the Toll-Like Receptor 2 Agonist Pam₃Cys

Carl O. Deetz,^1,2 Andrew M. Hebbeler,^1,3 Nadia A. Propp,¹ Cristiana Cairo,¹ Illia Tikhonov,^1, and C. David Pauza^1*

Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland,¹ Graduate Program in Molecular Medicine, University of Maryland, Baltimore, Maryland,² Department of Molecular Microbiology and Immunology, University of Maryland, Baltimore, Maryland³

Received 17 January 2006/ Returned for modification 3 March 2006/ Accepted 4 May 2006

Circulating V2V2 T-cell populations in healthy human beings are poised for rapid responses to bacterial or viral pathogens. We asked whether V2V2 T cells use the Toll-like receptor (TLR) family to recognize pathogen-associated molecular pattern molecules and to regulate cell functions. Analysis of expanded V2V2 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 V2V2 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 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 V2V2 T-cell responses at the site of infection and promote the rapid development of subsequent acquired antipathogen immunity.

Editor: J. F. Urban, Jr.

Present address: Sanofi Pasteur, Swiftwater, Pa.

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