FTY720 impairs CD8 T-cell function independently of the sphingosine-1-phosphate pathway

@article{Ntranos2014FTY720IC,
  title={FTY720 impairs CD8 T-cell function independently of the sphingosine-1-phosphate pathway},
  author={Achilles Ntranos and Olivia J Hall and Dionne P. Robinson and Inna V. Grishkan and Jason T. Schott and Dominique M Tosi and Sabra L. Klein and Peter A. Calabresi and Anne R. Gocke},
  journal={Journal of Neuroimmunology},
  year={2014},
  volume={270},
  pages={13-21}
}

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References

SHOWING 1-10 OF 41 REFERENCES

FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration.

Results indicate that FTY 720 exhibits not only a prophylactic but also a therapeutic effect on EAE in rats and mice, and that the effect of FTY720 appears to be due to a reduction of the infiltration of myelin antigen-specific CD4(+) T cells into the inflammation site.

Sphingosine Kinase 2 Is Required for Modulation of Lymphocyte Traffic by FTY720*

Although FTY720 was selectively activated in vivo by SPHK2, other S1P pro-drugs can be phosphorylated to cause lymphopenia through the action of additional sphingosine kinases.

Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720.

The generation of sphingosine kinase 2 (SPHK2) knockout mice is reported on and it is demonstrated that this enzyme is essential for FTY720 phosphate formation in vivo, indicating that SPHK2 is constantly required to maintain FTY 720 phosphate levels in vivo.

FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system

FTY720 may act through immune‐based and central mechanisms to reduce inflammation and support structural restoration of the central nervous system parenchyma and short‐term, low‐dose administration of FTY720 could help treat chronic (viral) infections.

Myelin Antigen-Specific CD8+ T Cells Are Encephalitogenic and Produce Severe Disease in C57BL/6 Mice1

It is reported that synthetic peptides 35–55 from myelin oligodendrocyte glycoprotein (pMOG35–55) consistently activate a high proportion of CD8+ αβTCR+ T cells that are encephalitogenic in C57BL/6 (B6) mice.

Pathogenic CD8 T Cells in Multiple Sclerosis and Its Experimental Models

Understanding how CNS-reactive CD8 T cells escape tolerance induction and induce CNS autoimmunity is critical to the ability to propose and test new therapies for MS.

Sphingosine 1-phosphate receptor agonists attenuate relapsing–remitting experimental autoimmune encephalitis in SJL mice

Kv1.3 Deletion Biases T Cells toward an Immunoregulatory Phenotype and Renders Mice Resistant to Autoimmune Encephalomyelitis

Skewing of CD4+ T cell differentiation toward Ag-specific regulatory T cells by pharmacological blockade or genetic suppression of Kv1.3 might be beneficial for therapy of immune-mediated diseases such as multiple sclerosis.