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In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse
Published on: October 25, 2024
Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis
M Mehling1, R Lindberg, F Raulf
1Department of Neurology, University Hospitals Basel, Petersgraben 4, CH-4031 Basel, Switzerland.
Neurology
|July 2, 2010
Summary
FTY720 significantly reduces interleukin-17 (IL-17)-producing T helper 17 (Th17) cells in multiple sclerosis (MS) patients. These Th17 cells, crucial for MS inflammation, are primarily central memory T cells impacted by FTY720 treatment.
Area of Science:
- Immunology
- Neuroimmunology
- Cellular Immunology
Background:
- Sphingosine 1-phosphate (S1P) receptor modulators like FTY720 are effective in multiple sclerosis (MS).
- FTY720 reduces circulating T cells by inhibiting their egress from lymphoid organs.
- The role and phenotype of interleukin-17 (IL-17)-producing T helper 17 (Th17) cells in MS and their response to FTY720 are not fully understood.
Purpose of the Study:
- To determine the phenotype and frequency of Th17 cells in patients with MS undergoing different treatments.
- To investigate how FTY720 treatment affects Th17 cell populations in the blood.
- To elucidate the relationship between Th17 cells and T cell memory subsets.
Main Methods:
- Prospective observational study design.
- Phenotypic characterization and enumeration of circulating T cells and Th17 cells.
- In vitro assessment of IL-17 production and RORC2 expression in T cell subsets.
Main Results:
- Th17 cells were predominantly identified within the central memory T cell subset across all groups.
- FTY720 treatment led to a >90% reduction in blood central memory T cells, including RORC2+ and IL-17-producing cells.
- FTY720 did not directly inhibit IL-17 production in activated T cells in vitro.
Conclusions:
- Phenotypic Th17 cells are characterized by a central memory T cell phenotype.
- FTY720 effectively reduces the number of Th17 cells in the peripheral blood.
- The reduction in Th17 cells is likely due to FTY720-induced retention of central memory T cells within secondary lymphoid organs.
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