Cyclosporin A increases IFN-gamma production by T cells when co-stimulated through CD28.
Eur J Immunol
; 28(5): 1481-91, 1998 May.
Article
em En
| MEDLINE
| ID: mdl-9603452
ABSTRACT
Despite its calcineurin-inhibiting properties, cyclosporin A (CsA) can not inhibit IL-2 production when T cells are co-stimulated by CD80/CD86 on the antigen-presenting cells. We studied the in vitro effect of CsA on IFN-gamma production. Anti-CD3 monoclonal antibody (mAb) was used as the primary stimulus for activation of purified human T cells. A stimulating anti-CD28 mAb, or CD80 or CD86 on stably transfected P815 cells, provided the co-stimulatory signal. IL-2 production was hardly affected by CsA under these stimulating conditions, while IFN-gamma (at the protein and mRNA level) was markedly stimulated by CsA. The use of anti-CD3 or phorbol 12-myristate 13-acetate with ionomycin as the primary stimulus, together with costimulation through either CD28 or CD2 using transfectants with the appropriate ligands, allowed us to demonstrate that the resistance of IFN-gamma production to inhibition by CsA required both CD3 and CD28 triggering. Inhibition of IL-10 production, and to a lesser degree of IL-4 production, by CD4+ cells was responsible for the enhancement of IFN-gamma production in the presence of CsA. In conclusion, IFN-gamma production by CD28-co-stimulated CD4+ T cells is resistant to inhibition by CsA and can even be facilitated by CsA as a result of removing a negative regulatory signal which is mainly IL-10 mediated. This finding might have implications for immunosuppressive strategies based upon the use of CsA.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T
/
Adjuvantes Imunológicos
/
Interferon gama
/
Ciclosporina
/
Antígenos CD28
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Bélgica