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Immunosuppressant FTY720 inhibits thymocyte emigration.
1Division of Immunology and Embryology, Department of Cell Biology, Tohoku University School of Medicine, Sendai, Japan.
European Journal of Immunology
|May 23, 2000
Summary
FTY720, an immunosuppressive drug, was found to inhibit T cell export from the thymus. This drug reduces T cell numbers in peripheral blood and lymph nodes, impacting T cell emigration.
Area of Science:
- Immunology
- Cellular Biology
- Pharmacology
Background:
- The thymus is crucial for supplying mature T cells to the peripheral immune system.
- Mechanisms of T cell export from the thymus are not fully understood.
Purpose of the Study:
- To investigate the effect of the novel immunosuppressive reagent FTY720 on T cell export from the thymus.
- To determine if FTY720 inhibits T cell emigration.
Main Methods:
- Mice were administered FTY720 daily at 1 mg/kg.
- Peripheral blood T lymphocyte counts were analyzed.
- Thymocyte populations were analyzed phenotypically (e.g., CD4, CD8, TCRαβ, L-selectin).
- Intrathymic labeling with fluorescein isothiocyanate was performed to track cell migration.
Main Results:
- FTY720 significantly decreased peripheral blood T lymphocyte numbers.
- In the thymus, FTY720 increased mature medullary thymocytes (CD4+CD8- and CD4-CD8+) and decreased double-positive cells (CD4+CD8+).
- Increased thymocyte subsets showed high L-selectin expression, suggesting retention within the thymus.
- Intrathymic cell tracking showed reduced migration to lymph nodes and spleen in FTY720-treated mice.
Conclusions:
- FTY720 inhibits T cell emigration from the thymus.
- This inhibition of T cell export contributes to the immunosuppressive action of FTY720.
- FTY720's mechanism of action involves blocking T cell migration from the thymus to the periphery.