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The Journal of Immunology, 2008, 181, 174-185
Copyright © 2008 by The American Association of Immunologists, Inc.
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Coligation of the Hepatitis C Virus Receptor CD81 with CD28 Primes Naive T Lymphocytes to Acquire Type 2 Effector Function1

Alessandro Serra2,*, Sandra Nuti*, Simona Tavarini*, Chiara Sammicheli*, Domenico Rosa*, Giulietta Saletti*, Elisabetta Soldaini*, Sergio Abrignani{dagger} and Andreas Wack3,*

* Novartis Vaccines, Siena, Italy; and {dagger} National Institute of Molecular Genetics, Milan, Italy

Costimuli provide supplementary signals required by naive T cells to become fully activated upon Ag encounter. Tetraspanins are a large family of transmembrane proteins that can costimulate T cells when engaged in vitro. In this study, we describe for the first time that coligation of the tetraspanins CD81, CD82, or CD9 with the costimulatory molecule CD28 in vitro leads to proliferation of naive T cells. When activated through this pathway, both CD4+ and CD8+ naive T cells differentiate into type 2 effector cells, which produce IL-4, IL-5, IL-13, and IL-10, together with IL-2 and TNF-{alpha}, but little to no IFN-{gamma}. These effector cells descend from precursors that display early and strong production of IL-4, STAT6 phosphorylation, and up-regulation of the transcription factor GATA-3, suggesting a direct skewing toward Th2 differentiation without a Th0 intermediate. The hepatitis C virus envelope protein E2 is the only ligand known for CD81. Therefore, we propose that this new type of Ag-independent T cell activation may occur in hepatitis C virus-infected individuals, contributing to liver inflammation, impaired type 1 immune responses, and recurrent flares of type 2 immunity associated with chronic infection.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by funding from Novartis Vaccines.

2 Current address: Cell Biology Group, Deutsches Rheumaforschungszentrum (DRFZ) Berlin, Charitéplatz 1, Berlin, Germany.

3 Address correspondence and reprint requests to Dr. Andreas Wack, Department of Molecular Immunology, Novartis Vaccines Research Center, Via Fiorentina 1, 53100 Siena, Italy. E-mail address: andreas.wack{at}novartis.com

4 Abbreviations used in this paper: HCV, hepatitis C virus; CD62L, L-selectin; TCO, T cells stimulated by CD28 and CD81 coengagement.


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The JI 2008 181: 3-4. [Full Text]  





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