| Literature DB >> 10092088 |
C Pioli1, L Gatta, D Frasca, G Doria.
Abstract
Purified CD4+ cells from the spleens of C57BL/6 mice were stimulated with anti-CD3, anti-CD28 and anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibodies. The results show that CTLA-4 stimulation inhibits IL-2 production induced by CD3-CD28 co-stimulation. Since CD3-CD28 co-stimulation induces IkappaBalpha degradation and consequently activates RelA, an NFkappaB family member relevant for the induction of IL-2 mRNA transcription, we tested whether the inhibitory effect of CTLA-4 stimulation interferes with this mechanism. CD3-CD28 co-stimulation was found to induce a drastic decrease in cytoplasmic IkappaBalpha and increase in nuclear RelA. CTLA-4 stimulation abrogates this effect of co-stimulation by increasing the level of cytoplasmic IkappaBalpha and decreasing the nuclear RelA level and DNA-binding activity. In conclusion, our results indicate that the inhibitory effect of CTLA-4 engagement on cytokine production correlates with prevention of IkappaBalpha degradation and inhibition of RelA nuclear translocation.Entities:
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Year: 1999 PMID： 10092088 DOI： 10.1002/(SICI)1521-4141(199903)29:03<856::AID-IMMU856>3.0.CO;2-P
Source DB: PubMed Journal: Eur J Immunol ISSN： 0014-2980 Impact factor: 5.532