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Coligation of the hepatitis C virus receptor CD81 with CD28 primes naive T lymphocytes to acquire type 2 effector function.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Jul 01; Vol. 181 (1), pp. 174-85. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes cytology
CD8-Positive T-Lymphocytes metabolism
Cell Differentiation immunology
Cell Membrane immunology
Cell Proliferation
Cells, Cultured
Cytokines immunology
Cytokines metabolism
Humans
Immunologic Memory immunology
Lymphocyte Activation immunology
Protein Binding
Tetraspanin 28
Antigens, CD immunology
CD28 Antigens immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Hepacivirus immunology
Immunity, Innate immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 181
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 18566382
- Full Text :
- https://doi.org/10.4049/jimmunol.181.1.174