Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse.
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.
Muñoz
Pilar
P
Departamento de Biología Celular e Immunología, Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Armilla, Spain.
Mittelbrunn
María
M
de la Fuente
Hortensia
H
Pérez-Martínez
Manuel
M
García-Pérez
Angélica
A
Ariza-Veguillas
Adriana
A
Malavasi
Fabio
F
Zubiaur
Mercedes
M
Sánchez-Madrid
Francisco
F
Sancho
Jaime
J
D051997:ADP-ribosyl Cyclase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D011992:Endosomes / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007152:Immunologic Capping / Q000235:genetics / Q000276:immunology*; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D011493:Protein Kinase C; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1