Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse.
Blood
; 111(7): 3653-64, 2008 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-18212246
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Membrane Glycoproteins
/
T-Lymphocytes
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Hemagglutinin Glycoproteins, Influenza Virus
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Calcium Signaling
/
ADP-ribosyl Cyclase 1
/
Immunologic Capping
/
Antigen-Presenting Cells
/
Antigens, Viral
Limits:
Humans
Language:
En
Journal:
Blood
Year:
2008
Document type:
Article
Affiliation country:
Spain