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
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