The pyrimidin analogue cyclopentenyl cytosine induces alloantigen-specific non-responsiveness of human T lymphocytes
| Autor: | R. A. W. Van Lier, S. L. Yong, I. J. M. ten Berge, F. J. Bemelman, Natalia Nikolaeva, A. Verschuur |
|---|---|
| Přispěvatelé: | Amsterdam institute for Infection and Immunity, Nephrology, Experimental Immunology, Cancer Center Amsterdam, Amsterdam Public Health, Paediatric Oncology, Landsteiner Laboratory |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cytotoxicity Immunologic Isoantigens Immunology Dose-Response Relationship Immunologic Apoptosis Mice Inbred Strains chemical and pharmacologic phenomena Cytidine CD8-Positive T-Lymphocytes Biology Lymphocyte Activation Cyclopentenyl Cytosine Mice Basic Immunology T-Lymphocyte Subsets Animals Humans Immunology and Allergy IL-2 receptor Enzyme Inhibitors Cells Cultured Cell Proliferation Clonal Anergy Graft Survival FOXP3 hemic and immune systems Skin Transplantation T lymphocyte Granzyme B Perforin Granzyme A biology.protein Immunosuppressive Agents CD8 |
| Zdroj: | Clinical and experimental immunology, 151(2), 348-358. Wiley-Blackwell |
| ISSN: | 0009-9104 |
| DOI: | 10.1111/j.1365-2249.2007.03557.x |
| Popis: | Summary Cyclopentenyl cytosine (CPEC) has been shown to induce apoptosis in human T lymphoblastic cell lines and T cells from leukaemia patients. In this study we have addressed the question of whether CPEC is able to decrease proliferation and effector functions of human alloresponsive T lymphocytes and induce T cell anergy. The proliferative capacity of human peripheral blood mononuclear cells in response to allogeneic stimulation was measured by 5,6-carboxy-succinimidyl-diacetate-fluorescein-ester staining. Flow cytometric analysis was performed using surface CD4, CD8, CD25, CD103 and intracellular perforin, granzyme A, granzyme B, caspase-3 and forkhead box P3 (FoxP3) markers. The in vivo immunosuppressive capacity was tested in a murine skin graft model. Addition of CPEC at a concentration of 20 nM strongly decreased the expansion and cytotoxicity of alloreactive T cells. Specific restimulation in the absence of CPEC showed that the cells became anergic. The drug induced caspase-dependent apoptosis of alloreactive T lymphocytes. Finally, CPEC increased the percentage of CD25high FoxP3+ CD4+ and CD103+ CD8+ T cells, and potentiated the effect of rapamycin in increasing the numbers of alloreactive regulatory T cells. Treatment with CPEC of CBA/CA mice transplanted with B10/Br skin grafts significantly prolonged graft survival. We conclude that CPEC inhibits proliferation and cytotoxicity of human alloreactive T cells and induces alloantigen non-responsiveness in vitro. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|