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 cc-stimulation. Since CD3-CD28 co-stimulation induces IκBα degradation and consequently activates RelA, an NfκB 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 IκBα and increase in nuclear RelA. CTLA-4 stimulation abrogates this effect of co-stimulation by increasing the level of cytoplasmic IκBα 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 IκBα degradation and inhibition of RelA nuclear translocation.
|Pages (from-to)||856 - 863|
|Number of pages||8|
|Journal||European Journal of Immunology|
|Publication status||Published - 1999|
All Science Journal Classification (ASJC) codes
Pioli, C., Gatta, L., Frasca, D., & Doria, G. (1999). Cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibits CD28-induced IκBα degradation and RelA activation. European Journal of Immunology, 29(3), 856 - 863.