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Cyclosporin A therapy differently affects immunological-relevant gene expression following immunization
Laurent Mascarell1, Paolo Truffa-Bachi
1Unité Biologie des Populations Lymphocytaires, Department of Immunology, CNRS URA 1961, Institut Pasteur, F-75724 Paris Cedex 15, France.
Abstract:
We have studied the effect of cyclosporin A (CSA) on the expression of genes involved in the immune response in mice bearing a transgenic T cell receptor specific for the peptide 88-104 of the pigeon cytochrome c. Immunization of mice treated with CSA resulted in the blockade of the IL2, IFN-gamma, CXCR-5, CCR-5 and CD25 gene transcription. CSA decreased the density of CD69 on T-cells but did not interfere with the induction of the chemokine receptors CCR-1, CCR-4, CXCR2 and CXCR-4. Finally, CSA accelerated the kinetics of CD44 and CD62L expression or re-expression and increased the density of both markers on T-cell membrane. The present data show that priming in presence of CSA resulted in the acquisition of a particular phenotype by the activated T-cells.
Insights
Cyclosporin A (CSA) treatment blocks key immune gene transcription, including IL-2 and IFN-gamma, and alters T-cell surface markers. This results in activated T-cells with a distinct phenotype, impacting immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Cyclosporin A (CSA) is an immunosuppressive drug widely used in transplantation and autoimmune diseases.
- Understanding CSA's precise molecular effects on immune cell gene expression is crucial for optimizing its therapeutic use.
Purpose of the Study:
- To investigate the impact of Cyclosporin A (CSA) on the gene expression profile of activated T-cells in a transgenic mouse model.
- To characterize the phenotypic changes in T-cells following priming in the presence of CSA.
Main Methods:
- Utilized a transgenic mouse model with a T cell receptor specific for pigeon cytochrome c peptide 88-104.
- Administered CSA to mice prior to immunization and analyzed gene transcription (IL-2, IFN-gamma, CXCR-5, CCR-5, CD25) and cell surface marker expression (CD69, CCR-1, CCR-4, CXCR2, CXCR-4, CD44, CD62L) via flow cytometry and gene expression analysis.
Main Results:
- CSA treatment led to the blockade of IL-2, IFN-gamma, CXCR-5, CCR-5, and CD25 gene transcription.
- CSA decreased CD69 expression on T-cells but did not affect CCR-1, CCR-4, CXCR2, or CXCR-4 induction.
- CSA accelerated the expression kinetics and increased the density of CD44 and CD62L on T-cell membranes.
Conclusions:
- Priming T-cells in the presence of CSA results in a distinct activated T-cell phenotype.
- CSA significantly modulates immune gene expression and T-cell surface marker profiles, influencing immune cell activation and function.