| Title | Cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibits CD28-induced IκBα degradation and RelA activation |
|---|---|
| Publication Type | Articolo su Rivista peer-reviewed |
| Year of Publication | 1999 |
| Authors | Pioli, Claudio, Gatta L., Frasca D., and Doria G. |
| Journal | European Journal of Immunology |
| Volume | 29 |
| Pagination | 856-863 |
| ISSN | 00142980 |
| Keywords | Animals, Antigens, article, Biological Transport, CD, CD28, CD28 antigen, CD3 antigen, CD4-Positive T-Lymphocytes, Cell Nucleus, Cytotoxic, cytotoxic T lymphocyte, cytotoxic T lymphocyte antigen 4, Differentiation, DNA, DNA-Binding Proteins, I-kappa B Proteins, Immunoconjugates, immunoglobulin enhancer binding protein, Inbred C57BL, interleukin 2, Interleukin-2, messenger RNA, Mice, NF-kappa B, priority journal, T-Lymphocytes, transcription factor RelA |
| 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 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. |
| Notes | cited By 23 |
| URL | https://www.scopus.com/inward/record.uri?eid=2-s2.0-0033024389&partnerID=40&md5=ed76c9d300eee41f7f02b3b8a37551b0 |
| Citation Key | Pioli1999856 |
