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T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
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FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis.

M Mehling1, V Brinkmann, J Antel

  • 1Department of Biomedicine and Neurology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland.

Neurology
|October 15, 2008
PubMed
Summary

FTY720 treatment for multiple sclerosis reduces naive and central memory T cells in blood. Remaining T cells maintain function, suggesting FTY720 traps specific T cell subsets in lymph nodes.

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Area of Science:

  • Immunology
  • Neuroscience
  • Pharmacology

Background:

  • Relapsing multiple sclerosis (MS) is treated with oral immunomodulator FTY720.
  • FTY720 inhibits T cell egress from lymphoid organs by antagonizing sphingosine 1-phosphate receptor-1 (S1P1).
  • The phenotype and function of T cells during long-term FTY720 treatment remain unclear.

Purpose of the Study:

  • To investigate the phenotype and function of T cells in peripheral blood of MS patients undergoing long-term FTY720 treatment.
  • To compare T cell populations in FTY720-treated patients with those treated with interferon-beta or untreated patients, and healthy donors.

Main Methods:

  • Analysis of T cell subpopulation composition, proliferation, and cytokine production.
  • Comparison of T cells from FTY720-treated MS patients, interferon-beta-treated MS patients, untreated MS patients, and healthy donors.

Main Results:

  • FTY720 treatment significantly reduced CD4+ and CD8+ T cell counts in peripheral blood.
  • Selective reduction of naive and central memory T cells (TCM), with a relative increase in effector memory T cells (TEM/TEMRA).
  • Remaining T cells showed reduced IL-2 secretion and proliferation but rapid interferon-gamma production upon reactivation; FTY720 did not directly suppress T cell function.

Conclusions:

  • Therapeutic FTY720 reduces naive and TCM in blood, sparing TEM.
  • The homing receptor CCR7 on naive T cells and TCM facilitates their trapping in lymph nodes by FTY720.
  • FTY720 treatment alters T cell distribution without impairing overall T cell function.