Production of TNF-α by Human Vγ9Vδ2 T Cells Via Engagement of FcγRIIIA, the Low Affinity Type 3 Receptor for the Fc Portion of IgG, Expressed upon TCR Activation by Nonpeptidic Antigen
Autor: | Virginie Lafont, Jean Pierre Liautard, Jean Favero, Janny Liautard |
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Rok vydání: | 2001 |
Předmět: |
Time Factors
MAP Kinase Signaling System T cell MAP Kinase Kinase 2 Immunology Down-Regulation Biology Lymphocyte Activation p38 Mitogen-Activated Protein Kinases Interleukin 21 Hemiterpenes Organophosphorus Compounds Antigens CD T-Lymphocyte Subsets medicine Humans Immunology and Allergy Cytotoxic T cell Lectins C-Type IL-2 receptor Phosphorylation Antigen-presenting cell Cells Cultured Mitogen-Activated Protein Kinase Kinases Antigens Bacterial Membrane Glycoproteins Tumor Necrosis Factor-alpha Immune Sera ZAP70 Receptors IgG Antibodies Monoclonal Receptors Antigen T-Cell gamma-delta Protein-Tyrosine Kinases Natural killer T cell Immunoglobulin Fc Fragments Cell biology medicine.anatomical_structure Receptor-CD3 Complex Antigen T-Cell Immunoglobulin G Interleukin 12 Tyrosine Mitogen-Activated Protein Kinases NK Cell Lectin-Like Receptor Subfamily D |
Zdroj: | The Journal of Immunology. 166:7190-7199 |
ISSN: | 1550-6606 0022-1767 |
Popis: | Human lymphocytes expressing the gammadelta TCR represent a minor T cell subpopulation found in blood. The majority of these cells express Vgamma9Vdelta2 determinants and respond to nonpeptidic phosphoantigens. Several studies have shown that, in vivo, the percentage of Vgamma9Vdelta2 T cells dramatically increases during pathological infection, leading to the hypothesis that they play an important role in the defense against pathogens. However, the specific mechanisms involved in this response remain poorly understood. It has been established that Vgamma9Vdelta2 T cells display potent cytotoxic activity against virus-infected and tumor cells, thereby resembling NK cells. In this study, we show that, upon stimulation by nonpeptidic Ags, Vgamma9Vdelta2 T cells express FcgammaRIIIA (CD16), a receptor that is constitutively expressed on NK cells. CD16 appears to be an activation Ag for Vgamma9Vdelta2 T cells. Indeed, ligation of CD16 on Vgamma9Vdelta2 T cells leads to TNF-alpha production. This TNF-alpha production, which is dependent (like that induced via the TCR-CD3 complex) on the activation of the p38 and extracellular signal-regulated kinase-2 mitogen-activated protein kinases, can be modulated by CD94 NK receptors. Therefore, it appears that Vgamma9Vdelta2 T cells can be physiologically activated by two sequential steps via two different cell surface Ags: the TCR-CD3 complex and the FcgammaRIIIA receptor, which are specific cell surface Ags for T lymphocytes and NK cells, respectively. This strongly suggests that, in the general scheme of the immune response, Vgamma9Vdelta2 T cells represent an important subpopulation of cells that play a key role in the defense against invading pathogens. |
Databáze: | OpenAIRE |
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