title: Distinct properties of circulating CD8+ T cells in FTY720-treated patients with multiple sclerosis.
abstract: 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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Montreal Neurological Institute, QC, Canada.
authors.forename: Trina A
authors.initials: TA
authors.lastname: Johnson
authors.forename: Yves
authors.initials: Y
authors.lastname: Lapierre
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000145:classification* / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D002465:Cell Movement / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000068876:Fingolimod Hydrochloride; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D054390:Receptors, CCR2 / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C515334:CCR2 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D016207:Cytokines; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D054390:Receptors, CCR2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine