PMID- 21543472 OWN - NLM STAT- MEDLINE DCOM- 20110915 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 85 IP - 14 DP - 2011 Jul TI - Role of CD4+ and CD8+ T-cell responses against JC virus in the outcome of patients with progressive multifocal leukoencephalopathy (PML) and PML with immune reconstitution inflammatory syndrome. PG - 7256-63 LID - 10.1128/JVI.02506-10 [doi] AB - Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the brain caused by JC virus (JCV). To assess the role of CD4(+) and CD8(+) T-cells against JCV in the clinical outcome of PML and PML in the setting of immune reconstitution inflammatory syndrome (IRIS), we tested gamma interferon (IFN-gamma) response by enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) in 117 subjects, including 66 PML patients with different clinical outcomes. Both assays were concordant and demonstrated that the cellular immune response against JCV is associated with better clinical outcome. PML survivors had an early CD8(+) T-cell response more frequently than PML progressors (100% versus 27.3%; P = 0.001), while only a trend was observed for the early CD4(+) T-cell response between these two groups (80% versus 45.5%; P = 0.18). Although IRIS itself was more frequent in the PML survivor group, there was no difference in IFN-gamma-producing CD4(+) and CD8(+) T-cells between IRIS and non-IRIS PML patients, suggesting that T-cells expressing other cytokines likely have a role in the immunopathogenesis of IRIS. ELISpot and ICS assays are useful prognostic markers of PML evolution and may help in the clinical management of these patients. FAU - Gheuens, Sarah AU - Gheuens S AD - Division of NeuroVirology, Beth Israel Deaconess Medical Center, E/CLS-1005, 330 Brookline Avenue, Boston, MA 02215, USA. FAU - Bord, Evelyn AU - Bord E FAU - Kesari, Santosh AU - Kesari S FAU - Simpson, David M AU - Simpson DM FAU - Gandhi, Rajesh T AU - Gandhi RT FAU - Clifford, David B AU - Clifford DB FAU - Berger, Joseph R AU - Berger JR FAU - Ngo, Long AU - Ngo L FAU - Koralnik, Igor J AU - Koralnik IJ LA - eng GR - T32 AI007387/AI/NIAID NIH HHS/United States GR - K24 NS 060950/NS/NINDS NIH HHS/United States GR - R56 NS041198/NS/NINDS NIH HHS/United States GR - R56 NS 041198/NS/NINDS NIH HHS/United States GR - R01 NS 047029/NS/NINDS NIH HHS/United States GR - UL1 RR 025758/RR/NCRR NIH HHS/United States GR - P30 AI060354/AI/NIAID NIH HHS/United States GR - T32 CA09031-32/CA/NCI NIH HHS/United States GR - P30 AI60354/AI/NIAID NIH HHS/United States GR - UL1 RR025758/RR/NCRR NIH HHS/United States GR - T32 CA009031/CA/NCI NIH HHS/United States GR - R01 NS047029/NS/NINDS NIH HHS/United States GR - K24 NS060950/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110504 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 SB - IM MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Humans MH - Inflammation/*immunology MH - JC Virus/*immunology MH - Leukoencephalopathy, Progressive Multifocal/*immunology PMC - PMC3126613 EDAT- 2011/05/06 06:00 MHDA- 2011/09/16 06:00 PMCR- 2012/01/01 CRDT- 2011/05/06 06:00 PHST- 2011/05/06 06:00 [entrez] PHST- 2011/05/06 06:00 [pubmed] PHST- 2011/09/16 06:00 [medline] PHST- 2012/01/01 00:00 [pmc-release] AID - JVI.02506-10 [pii] AID - 2506-10 [pii] AID - 10.1128/JVI.02506-10 [doi] PST - ppublish SO - J Virol. 2011 Jul;85(14):7256-63. doi: 10.1128/JVI.02506-10. Epub 2011 May 4.