Distinct properties of circulating CD8+ T cells in FTY720-treated patients with multiple sclerosis

Arch Neurol. 2010 Dec;67(12):1449-55. doi: 10.1001/archneurol.2010.312.


Objective: To define the capacity of peripheral blood CD8(+) T cells from patients with multiple sclerosis (MS) receiving fingolimod (FTY720) to migrate in response to chemokines that contribute to trafficking into the central nervous system.

Design: Peripheral blood T cells of FTY720-treated patients with MS (MS-FTY) are mainly CD8(+) CCR7⁻ effector memory cells as CCR7(+) T cells are inhibited from exiting from secondary lymph nodes. Migration of CD8(+) T cells from MS-FTY patients and untreated donors to chemokines CXCL12 and CCL2 was assayed in vitro. Expression of CCL2 receptor (CCR2), CCR7, CD28, and CD27 on CD8(+) T cells was determined by flow cytometry.

Setting: Montreal Neurological Institute's clinical research unit. Patients The MS-FTY patients were part of the extension phase of FTY720 clinical trials for relapsing-remitting MS.

Results: In vitro addition of active (phosphorylated) FTY720 increased migration of CD8(+) T cells from untreated patients to CXCL12 and CCL2. The CD8(+) or CD8(+) CCR7⁻ T cells from MS-FTY patients migrated less to CXCL12 and CCL2 compared with those from untreated donors. The proportion of CD8(+) CCR7⁻ cells that express the CCL2 chemokine receptor, CCR2, was significantly reduced in the MS-FTY group. The CD8(+) CCR7⁻ cells from the MS-FTY patients were enriched with CD27⁻ CD28⁻ (late effector) memory cells, a population with reduced expression of CCR2 compared with early (CD27(+) CD28(+)) effector memory cells.

Conclusions: Therapy with FTY720 results in a subset of CD8(+) T cells with distinct functional migratory properties dominating the peripheral circulation. The expected forthcoming use of FTY720 as a sustained therapy for MS will clarify how this redistribution of lymphocyte populations affects the overall process of immune surveillance.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / classification*
  • CD8-Positive T-Lymphocytes / drug effects
  • Cell Count / methods
  • Cell Movement / drug effects*
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL12 / metabolism
  • Cytokines / metabolism
  • Fingolimod Hydrochloride
  • Flow Cytometry / methods
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Interferon-gamma / metabolism
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Propylene Glycols / pharmacology*
  • Propylene Glycols / therapeutic use
  • Receptors, CCR2 / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology
  • Sphingosine / therapeutic use
  • Tumor Necrosis Factor-alpha / metabolism


  • CCR2 protein, human
  • Chemokine CCL2
  • Chemokine CXCL12
  • Cytokines
  • Immunosuppressive Agents
  • Propylene Glycols
  • Receptors, CCR2
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Fingolimod Hydrochloride
  • Sphingosine