title: JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathy.
abstract: Most immunosuppressed individuals who develop progressive multifocal leukoencephalopathy (PML) have a rapid fatal outcome, whereas some become long-term survivors. We explored the impact of the cellular immune response against JC virus (JCV) on the clinical outcome of 7 HIV+ and 3 HIV- individuals with PML. Of the 4 HIV+/PML survivors, all had detectable cytotoxic T lymphocytes (CTL) specific for JCV T or VP 1 proteins compared to none of the 3 HIV+/PML progressors tested. Of the 3 HIV-/PML patients, 1 was recently diagnosed with PML and showed evidence of neurologic improvement without any treatment. This patient had CTL specific for the VP1 protein of JCV. The other 2 HIV-/PML survivors were stable 3-8 years after the diagnosis of PML. They did not have any detectable CTL against JCV. These findings suggest that JCV-specific immune response is associated with favorable outcome in HIV+ individuals with PML. The lack of detectable JCV-specific CTL in 2 HIV-/PML survivors might indicate a burnt-out disease without sufficient antigenic stimulation to maintain the cellular immune response. The detection of JCV-specific CTL in an HIV- patient recently diagnosed with PML, who was showing evidence of neurological improvement without any treatment, indicates that this finding may be used as a favorable prognostic marker of disease evolution in the clinical management of patients with PML. As the quest for an effective treatment of PML continues, JCV-specific cellular immune response deserves further attention because it appears to play a crucial role in the prevention of disease progression.
authors.affiliation: Department of Neurology and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Du Pasquier
authors.forename: K W
authors.initials: KW
authors.lastname: Clark
authors.forename: P S
authors.initials: PS
authors.lastname: Smith
authors.forename: J T
authors.initials: JT
authors.lastname: Joseph
authors.forename: J M
authors.initials: JM
authors.lastname: Mazullo
authors.forename: U
authors.initials: U
authors.lastname: De Girolami
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
authors.forename: I J
authors.initials: IJ
authors.lastname: Koralnik
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000401:mortality / Q000821:virology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000401:mortality / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology* / Q000401:mortality / Q000821:virology; D011379:Prognosis; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology