FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disea...FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, （S）-enantiomer of FTY720-phosphate [（S）-FTY720-P] on experimental autoimmune encephalomyelitis （EAE） in rats and mice. Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE, and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4^＋ T cells into spinal cord was decreased by prophylactic treatment with FTY720 and （S）-FTY720-P. When FTY720 or （S）-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-β, and the area of demyelination and the infiltration of CD4^＋ T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4^＋ T cells into the inflammation site. Cellular ＆ Molecular Immunology. 2005;2（6）：439-448.展开更多
Pathogenic African swine fever virus(ASFV)remains a lethal causative agent in the domestic pig industry,which poses a burden on the swine market and causes substantial socioeconomic losses worldwide.Currently,there ar...Pathogenic African swine fever virus(ASFV)remains a lethal causative agent in the domestic pig industry,which poses a burden on the swine market and causes substantial socioeconomic losses worldwide.Currently,there are no commercially efcacious vaccines or specifc treatments available for ASF prevention and control.Unfortunately,little is known about the swine immune response upon ASFV infection.Here,we investigated the host immune response discrepancy induced by the feld moderately virulent strain ASFV HB-2208 among healthy,diseased and asymptomatic pigs.In the peripheral blood of diseased swine,lymphopenia is caused by the massive loss of bystander lymphocytes,such asγδT cells,B cells and CD4^(+)T cells.Conversely,ASFV has a strong tropism for the mononuclear phagocyte system(MPS)and partial dendritic cells(DCs),whose antigen-presenting ability is impeded by the downregulation of CD80 and MHC I.However,no signifcant diference in the number of CD8α^(high) T cells was detected,whereas the frequencies of NK cells,NKT cells,and regulatory T cells(Tregs)were signifcantly increased.Additionally,an in vitro model was established with a coculture of primary pulmonary alveolar macrophages(PAMs)and peripheral blood mononuclear cells(PBMCs),which signifcantly reducedγδT cells,B cells and CD4^(+)T cells and increased Tregs.The diferentiated immune response might aid in enhancing the understanding of ASFV pathogenesis in suids and provide insights into the mechanism of ASFV-induced lymphopenia for further studies.展开更多
文摘FTY720, a sphingosine 1-phosphate receptor modulator, induces a marked decrease in the number of peripheral blood lymphocytes and exerts immunomodulating activity in various experimental allograft and autoimmune disease models. In this study, we evaluated the effect of FTY720 and its active metabolite, （S）-enantiomer of FTY720-phosphate [（S）-FTY720-P] on experimental autoimmune encephalomyelitis （EAE） in rats and mice. Prophylactic administration of FTY720 at 0.1 to 1 mg/kg almost completely prevented the development of EAE, and therapeutic treatment with FTY720 significantly inhibited the progression of EAE and EAE-associated histological change in the spinal cords of LEW rats induced by immunization with myelin basic protein. Consistent with rat EAE, the development of proteolipid protein-induced EAE in SJL/J mice was almost completely prevented and infiltration of CD4^＋ T cells into spinal cord was decreased by prophylactic treatment with FTY720 and （S）-FTY720-P. When FTY720 or （S）-FTY720-P was given after establishment of EAE in SJL/J mice, the relapse of EAE was markedly inhibited as compared with interferon-β, and the area of demyelination and the infiltration of CD4^＋ T cells were decreased in spinal cords of EAE mice. Similar therapeutic effect by FTY720 was obtained in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. These results indicate that FTY720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 on EAE appears to be due to a reduction of the infiltration of myelin antigen-specific CD4^＋ T cells into the inflammation site. Cellular ＆ Molecular Immunology. 2005;2（6）：439-448.
基金support provided by the National Natural Sciences Foundation of China(Grant Nos.32172873 and 31941005)the National Programme on Key Research Project of China(2021YFD1800105-2)National Natural Sciences Foundation of China,32172873,Min Cui,31941005,Min Cui,National Programme on Key Research Project of China,2021YFD1800105-2,Min Cui。
文摘Pathogenic African swine fever virus(ASFV)remains a lethal causative agent in the domestic pig industry,which poses a burden on the swine market and causes substantial socioeconomic losses worldwide.Currently,there are no commercially efcacious vaccines or specifc treatments available for ASF prevention and control.Unfortunately,little is known about the swine immune response upon ASFV infection.Here,we investigated the host immune response discrepancy induced by the feld moderately virulent strain ASFV HB-2208 among healthy,diseased and asymptomatic pigs.In the peripheral blood of diseased swine,lymphopenia is caused by the massive loss of bystander lymphocytes,such asγδT cells,B cells and CD4^(+)T cells.Conversely,ASFV has a strong tropism for the mononuclear phagocyte system(MPS)and partial dendritic cells(DCs),whose antigen-presenting ability is impeded by the downregulation of CD80 and MHC I.However,no signifcant diference in the number of CD8α^(high) T cells was detected,whereas the frequencies of NK cells,NKT cells,and regulatory T cells(Tregs)were signifcantly increased.Additionally,an in vitro model was established with a coculture of primary pulmonary alveolar macrophages(PAMs)and peripheral blood mononuclear cells(PBMCs),which signifcantly reducedγδT cells,B cells and CD4^(+)T cells and increased Tregs.The diferentiated immune response might aid in enhancing the understanding of ASFV pathogenesis in suids and provide insights into the mechanism of ASFV-induced lymphopenia for further studies.
