Activation induces apoptosis inHerpesvirus saimiri-transformed T cells independent of CD95 (Fas, APO-1)
| Autor: | Jean-Pierre de Villartay, Bernhard Fleckenstein, Barbara M. Bröker, Edgar Meinl, Ulricke Klauenberg, Michael S. Kraft, Françoise Le Deist, Bernhard Fleischer |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
T cell
Immunology Apoptosis chemical and pharmacologic phenomena Biology Ligands Lymphocyte Activation Herpesvirus 2 Saimiriine chemistry.chemical_compound Interleukin 21 Immune system T-Lymphocyte Subsets medicine Humans Immunology and Allergy Cytotoxic T cell fas Receptor IL-2 receptor Phosphorylation Cell Line Transformed Tumor Necrosis Factor-alpha ZAP70 T-cell receptor Tyrosine phosphorylation Cell Transformation Viral Cell biology medicine.anatomical_structure chemistry Cyclosporine Tyrosine |
| Zdroj: | European Journal of Immunology. 27:2774-2780 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.1830271105 |
| Popis: | Signaling via the T cell receptor (TCR)/CD3 complex of pre-activated T cells induces apoptosis. Such an activation-induced cell death (AICD) is thought to play an important role in the regulation of cellular immune responses. In this study we analyzed pathways of AICD by using human T cells transformed by Herpesvirus saimiri. These growth-transformed T cells show the phenotype of activated mature T cells and continue to express a functionally intact TCR. We show that human H. saimiri-transformed T cell clones readily undergo cell death upon signaling via the TCR/CD3 complex or via phorbol 12-myristate 13-acetate (PMA) + ionomycin. The AICD in H. saimiri-transformed T cells was detectable a few hours after activation and it was not affected by the presence of interleukin (IL)-2 or by anti-CD4 cross-linking. However, AICD required tyrosine phosphorylation, since it could be blocked by herbimycin A. Cyclosporin A (CsA) did not block the development of AICD, but other consequences of activation in H. saimiri-transformed T cells like the production of interferon-gamma. Surprisingly, the development of AICD was not reduced by neutralizing antibodies to tumor necrosis factor (TNF)-alpha or blocking antibodies directed to CD95 (Fas, APO-1), although H. saimiri-transformed T cells were sensitive to CD95 ligation. To confirm that this form of AICD is really independent of CD95, we have established an H. saimiri-transformed T cell line from a patient with a homozygous deletion in the CD95 gene. This CD95-deficient T cell line was as sensitive to AICD as other CD95-expressing H. saimiri-transformed T cells. In conclusion, we describe here a type of AICD in H. saimiri-transformed T cells that is independent of CD95 and TNF-alpha, not sensitive to CsA, but requires tyrosine phosphorylation. This system should be useful for the investigation of CD95-independent forms of AICD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text