Evidence that FTY720 induces rat thymocyte apoptosis

Transplant Immunology
Naohito IsoyamaKatsusuke Naito

Abstract

FTY720, a novel immunomodulator with the potential to improve immunosuppressive therapy after organ transplantation, is currently under clinical investigation. FTY720 drastically decreases blood lymphocytes, especially T cells, accelerating lymphocyte homing to secondary lymphoid organs. However, its immunosuppressive effects remain unknown. We investigated these effects in rat thymocytes. Rats were intramuscularly injected with 10mg/kg/day FTY720 or saline for 7days. Thymuses were removed on days 0, 1, 3, 5, 7 and 14 after treatment. Three-color analysis was performed with a flow cytofluorometer. Apoptotic nuclei in the tissue sections were identified by TUNEL. Genomic DNA was then extracted and samples were electrophoresed on 2.0% agarose gel. FTY720 reduced the total number of thymocytes and, with time, significantly reduced the percentage of CD4+8+ TCRalphabeta(negative/low) thymocytes. Light microscopy of thymuses of FTY720-treated rats revealed obvious reductions in the size of the cortical region. TUNEL analysis showed that FTY720 induced thymocyte apoptosis in the cortical region. Furthermore, DNA fragmentation was observed in thymocytes treated with FTY720, indicating thymocyte apoptosis. FTY720 reduced the number of C...Continue Reading

References

Feb 1, 1995·The Journal of Experimental Medicine·J OgasawaraS Nagata
Jan 1, 1997·Clinical and Experimental Immunology·S SuzukiS Naoe
Jul 31, 1999·Immunopharmacology·Z J LuoM Miyasaka
Dec 20, 2000·Transplantation Proceedings·K TakaiK Naito
Feb 28, 2002·The Journal of Pharmacology and Experimental Therapeutics·Masayuki FujinoSeiichi Suzuki

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