Abstract
During immunologic synapse (IS) formation, human CD38 redistributes to the contact area of T cell-antigen-presenting cell (APC) conjugates in an antigen-dependent manner. Confocal microscopy showed that CD38 preferentially accumulated along the contact zone, whereas CD3-zeta redistributed toward the central zone of the IS. APC conjugates with human T cells or B cells transiently expressing CD38-green fluorescent protein revealed the presence of 2 distinct pools of CD38, one localized at the cell membrane and the other in recycling endosomes. Both pools were recruited to the T/APC contact sites and required antigen-pulsed APCs. The process appeared more efficient in T cells than in APCs. CD38 was actively recruited at the IS of T cells by means of Lck-mediated signals. Overexpression of CD38 in T cells increased the levels of antigen-induced intracellular calcium release. Opposite results were obtained by down-regulating surface CD38 expression by means of CD38 siRNA. CD38 blockade in influenza HA-specific T cells inhibited IL-2 and IFN-gamma production, PKC phosphorylation at Thr538, and PKC recruitment to the IS induced by antigen-pulsed APCs. These results reveal a new role for CD38 in modulating antigen-mediated T-cell responses during IS formation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-ribosyl Cyclase 1 / antagonists & inhibitors
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ADP-ribosyl Cyclase 1 / genetics
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ADP-ribosyl Cyclase 1 / immunology*
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology*
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Antigens, Viral / immunology*
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CD3 Complex / genetics
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CD3 Complex / immunology
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Calcium Signaling / genetics
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Calcium Signaling / immunology*
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Down-Regulation / genetics
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Down-Regulation / immunology
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Endosomes / genetics
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Endosomes / immunology
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Hemagglutinin Glycoproteins, Influenza Virus / immunology*
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Humans
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Immunologic Capping / genetics
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Immunologic Capping / immunology*
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Jurkat Cells
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / genetics
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / immunology
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Phosphorylation
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Protein Kinase C / genetics
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Protein Kinase C / immunology
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RNA, Small Interfering / genetics
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RNA, Small Interfering / immunology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
Substances
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Antigens, Viral
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CD3 Complex
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CD3 antigen, zeta chain
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Hemagglutinin Glycoproteins, Influenza Virus
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Membrane Glycoproteins
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RNA, Small Interfering
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Protein Kinase C
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CD38 protein, human
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ADP-ribosyl Cyclase 1