| First Author | Choi JM | Year | 2008 |
| Journal | Proc Natl Acad Sci U S A | Volume | 105 |
| Issue | 50 | Pages | 19875-80 |
| PubMed ID | 19066215 | Mgi Jnum | J:142668 |
| Mgi Id | MGI:3821924 | Doi | 10.1073/pnas.0805198105 |
| Citation | Choi JM, et al. (2008) Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis. Proc Natl Acad Sci U S A 105(50):19875-80 |
| abstractText | CTLA-4 (CD152) negatively regulates T cell activation signaling, and the cytoplasmic domain of CTLA-4 (ctCTLA-4) itself has the capacity to inhibit T cell activation in vitro and in vivo. In this study, the inhibitory mechanisms of the cell-permeable recombinant protein Hph-1-ctCTLA-4 on T cell activation and its ability to prevent collagen-induced arthritis were analyzed. Hph-1-ctCTLA-4 prevented human and mouse T cell activation and proliferation by inhibition of T cell receptor-proximal signaling and the arrest of the cell cycle. Furthermore, Hph-1-ctCTLA-4 protected human umbilical vein endothelial cells (HUVEC) from the human CTL allo-response. The incidence and severity of collagen-induced arthritis were significantly reduced and the erosion of cartilage and bone was effectively prevented by i.v. injection and transdermal administration of Hph-1-ctCTLA-4. Inflammatory cytokine production (IL-1beta, IL-6, TNF-alpha, IL-17A) and collagen-specific antibody levels were significantly reduced, and the numbers of activated T cells and infiltrating granulocytes were substantially decreased. These results demonstrate that systemic or transdermal application of a cell-permeable form of the cytoplasmic domain of CTLA-4 offers an effective therapeutic approach for autoimmune diseases such as rheumatoid arthritis. |
