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FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and
D D Pinschewer1, A F Ochsenbein, B Odermatt
1Institute of Experimental Immunology and Laboratory for Special Techniques, Department of Pathology, University Hospital, Zurich, Switzerland.
Journal of Immunology (Baltimore, Md. : 1950)
|May 23, 2000
Summary
FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride) reduces CD8+ T cell recruitment to peripheral lesions without impairing immune responses. This immunomodulatory effect may treat organ-specific T cell-mediated diseases.
Area of Science:
- Immunology
- Pharmacology
Background:
- FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride) is known to prolong allograft survival.
- The precise mechanisms underlying FTY720's immunomodulatory effects require further elucidation.
Purpose of the Study:
- To investigate the immunomodulatory mechanisms of FTY720 in viral infection models.
- To assess the impact of FTY720 on T cell responses, B cell responses, and anti-viral immunity.
Main Methods:
- Mice were infected with lymphocytic choriomeningitis virus (LCMV) or vesicular stomatitis virus.
- Oral administration of FTY720 (0.3 mg/kg/day) was employed.
- T cell responses, B cell responses, viral replication, delayed-type hypersensitivity reactions, and T cell infiltration were evaluated.
Main Results:
- FTY720 did not affect viral replication or the induction and expansion of specific CTL and B cells.
- A reversible shift of CTL distribution from spleen to lymph nodes and lymphocytopenia were observed.
- Delayed-type hypersensitivity reactions were reduced, with impaired circulation of effector lymphocytes and reduced tissue-infiltrating CTL.
- FTY720 delayed or prevented CD8+ T cell-mediated diabetes by reducing islet-infiltrating CTL.
Conclusions:
- FTY720 reduces CD8+ effector T cell recirculation and recruitment to peripheral lesions.
- Immune responses in secondary lymphoid organs remain unaffected by FTY720.
- FTY720 shows potential for treating ongoing organ-specific T cell-mediated immunopathologic diseases.