Cholera toxin B-subunit prevents activation and proliferation of human CD4+ T cells by activation of a neutral sphingomyelinase in lipid rafts.
J Immunol
; 175(9): 5637-48, 2005 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-16237053
ABSTRACT
The inhibition of human CD4+ T lymphocyte activation and proliferation by cholera toxin B-subunit (CTB) is a well-established phenomenon; nevertheless, the exact mechanism remained unclear. In the present study, we propose an explanation for the rCTB-induced inhibition of CD4+ T lymphocytes. rCTB specifically binds to GM1, a raft marker, and strongly modifies the lipid composition of rafts. First, rCTB inhibits sphingomyelin synthesis; second, it enhances phosphatidylcholine synthesis; and third, it activates a raft-resident neutral sphingomyelinase resembling to neutral sphingomyelinase type 1, thus generating a transient ceramide production. We demonstrated that these ceramides inhibit protein kinase Calpha phosphorylation and its translocation into the modified lipid rafts. Furthermore, we show that rCTB-induced ceramide production activate NF-kappaB. Combined all together raft modification in terms of lipids, ceramide production, protein kinase Calpha inhibition, and NF-kappaB activation lead to CD4+ T cell inhibition.
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Banco de datos:
MEDLINE
Asunto principal:
Esfingomielina Fosfodiesterasa
/
Activación de Linfocitos
/
Linfocitos T CD4-Positivos
/
Toxina del Cólera
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Microdominios de Membrana
Límite:
Adult
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia