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.