Abstract Details

Title Proportions and Functional Properties of Regulatory T Cells Are Enhanced by FTY720 in Patients with Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 154

Objective

Background BACKGROUND: A defect in the suppressive function of naturally occurring Treg has been implicated in the pathogenesis of MS. FTY720 is a sphingosine-1-phosphate (S1P) receptor agonist that was recently approved for treatment of relapsing remitting MS (RRMS). FTY720 inhibits lymphocyte egress from secondary lymphoid organs into the circulation and is likely to preclude trafficking of pathogenic lymphocytes into the central nervous system. Recent animal studies suggest that the immunomodulatory action of FTY720 also includes effects on Treg function and frequencies.

Design/Methods DESIGN/METHODS: We prospectively assessed frequencies and phenotypes of blood CD4+ T cells including Treg as well as suppressive activities of isolated Treg in patients with RRMS undergoing prolonged therapy with FTY720 (n=20) and in healthy donors (n=20). Experiments were completed by determination of S1P triggered trafficking of Treg using transwell assays.

Results RESULTS: Treatment with FTY720 (1-3 months) led to a massive reduction of blood CD4+ T cells (80-90%) which was mainly driven by selective decrease of CCR7 expressing subtypes. In contrast, relative frequencies of Treg were strongly (2-3-fold) increased without major changes in the distribution of naive, recent thymic emigrant (RTE) and memory Treg phenotypes. Concomitantly, FTY720 therapy improved the Treg inhibitory function on polyclonally stimulated conventional T cells in vitro.

Conclusions CONCLUSIONS: Our observations suggest that FTY720 exerts beneficial effects on the Treg compartment in MS. As circulating Treg do not become enriched in naive Treg subtypes that were previously shown to contribute to the overall Treg performance, the enhanced inhibitory activity is likely to be influenced by the depletion of activated CCR7+ T cells.

Authors/Disclosures
Juergen Haas PRESENTER	Juergen Haas has nothing to disclose.
Bettina Balint, MD (University Hospital of Zurich)	Dr. Balint has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Brigitte Wildemann, MD (University Hospital Heidelberg, Department of Neurology)	The institution of Dr. Wildemann has received research support from Roche. The institution of Dr. Wildemann has received research support from Novartis. The institution of Dr. Wildemann has received research support from Argenx. Dr. Wildemann has received personal compensation in the range of $500-$4,999 for serving as a Conference participant with Neuraxpharm. Dr. Wildemann has received personal compensation in the range of $0-$499 for serving as a Speaker with Roche. Dr. Wildemann has received personal compensation in the range of $0-$499 for serving as a Soeaker with Instand.

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