title: Impairment of JCV-specific T-cell response by corticotherapy: effect on PML-IRIS management?
abstract: OBJECTIVE
  To investigate the impact of corticosteroids (CS) on the viral-specific T-cell response, in particular the JC virus (JCV)-specific one, in an attempt to determine the optimal timing of CS in the management of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS).
  
  
  METHODS
  A blood draw was performed before and 7 days after the administration of IV CS to 24 patients with relapsing multiple sclerosis (MS). The phenotypic pattern of T cells was determined by CCR7 and CD45RA. To assess the impact of CS treatment on proliferative response of JCV-, influenza-, and Epstein-Barr virus (EBV)-specific T cells, a thymidine incorporation proliferation assay was performed. An intracellular cytokine staining assay was performed to determine the effect of CS treatment on the production of cytokine by virus-specific T cells. JCV T-cell assays were performed only in JCV-infected patients with MS as detected by serologies (Stratify) or detection of JCV DNA in the urine by PCR.
  
  
  RESULTS
  CS led T cells, CD4+ and CD8+, toward a less differentiated phenotype. There was a significant decrease of EBV-, influenza-, and JCV-specific T-cell proliferative response upon CS treatment. There was a significant decrease in the frequency of interferon (IFN) γ- and tumor necrosis factor (TNF) α-producing JCV-specific CD8+ T cells, but not EBV- or influenza-specific CD4+ or CD8+ T cells.
  
  
  CONCLUSIONS
  CS have a profound impact on the virus-specific T-cell response, especially on JCV, suggesting that when CS are considered, they should not be given before the onset of clinical or radiologic signs of IRIS. Studies addressing directly patients with MS with natalizumab-caused PML are warranted.
  
  
  METHODS
  This study provides Class III evidence that methylprednisolone treatment decreases the frequency of JCV-specific CD8+ T cells producing IFN-γ and TNFα, impairing control of JCV, suggesting this should be used to treat but not to prevent PML-IRIS. No clinical outcomes were measured.
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Antoniol
authors.forename: Samantha
authors.initials: S
authors.lastname: Jilek
authors.forename: Myriam
authors.initials: M
authors.lastname: Schluep
authors.forename: Noëlle
authors.initials: N
authors.lastname: Mercier
authors.forename: Mathieu
authors.initials: M
authors.lastname: Canales
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Goff
authors.forename: Claudia
authors.initials: C
authors.lastname: Campiche
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Renaud A
authors.initials: RA
authors.lastname: Du Pasquier
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007577:JC Virus / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D008775:Methylprednisolone