| Autor: |
Hoff H; Department of Pediatrics, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany., Knieke K, Cabail Z, Hirseland H, Vratsanos G, Burmester GR, Jorch G, Nadler SG, Bröker B, Hebel K, Brunner-Weinzierl MC |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2009 May 01; Vol. 182 (9), pp. 5342-51. |
| DOI: |
10.4049/jimmunol.0801624 |
| Abstrakt: |
CD28(null) T cells are a highly enriched subset of proinflammatory T cells in patients with autoimmune diseases that are oligoclonal and autoreactive. In this study, we analyzed the role of CD152 signaling on the longevity of human CD28(null) T cells. Using a sensitive staining method for CD152, we show that human CD4(+)CD28(null) and CD8(+)CD28(null) T cells rapidly express surface CD152. Serological inactivation of CD152 using specific Fab or blockade of CD152 ligands using CTLA-4Ig in CD4(+)CD28(null) and CD8(+)CD28(null) T cells enhances apoptosis in a Fas/FasL-dependent manner. CD152 cross-linking on activated CD28(null) cells prevents activation-induced cell death as a result of reduced caspase activity. Apoptosis protection conferred by CD152 is mediated by phosphatidylinositol 3'-kinase-dependent activation of the kinase Akt, resulting in enhanced phosphorylation and thereby inhibition of the proapoptotic molecule Bad. We show that signals triggered by CD152 act directly on activated CD28(null) T lymphocytes and, due to its exclusive expression as a receptor for CD80/CD86 on CD28(null) T cells, prevention of CD152-mediated signaling is likely a target mechanism taking place during therapy with CTLA-4Ig. Our data imply strongly that antagonistic approaches using CD152 signals for chronic immune responses might be beneficial. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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