JCV-specific cellular immune response correlates with a favorable clinicaloutcome in HIV-infected individuals with progressive multifocal leukoencephalopathy

Most immunosuppressed individuals who develop progressive multifocal leukoe ncephalopathy (PML) have a rapid fatal outcome, whereas some become long-te rm survivors. We explored the impact of the cellular immune response agains t JC virus (JCV) on the clinical outcome of 7 HIV+ and 3 HIV- individuals w ith PML. Of the 4 HIV+/PML survivors, all had detectable cytotoxic T lympho cytes (CTL) specific for JCV T or VP 1 proteins compared to none of the 3 H TV+/PML progressors tested. Of the 3 HIV-/PML patients, I was recently diag nosed with PML and showed evidence of neurologic improvement without any tr eatment. This patient had CTL specific for the VP1 protein of JCV. The othe r 2 HIV-/PML survivors were stable 3-8 years after the diagnosis of PML. Th ey did not have any detectable CTL against JCV. These findings suggest that JCV-specific immune response is associated with favorable outcome in HIVindividuals with PML. The lack of detectable JCV-specific CTL in 2 HIV-/PML survivors mi-ht 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 showin g evidence of neurological improvement without any treatment, indicates tha t this finding may be used as a favorable prognostic marker of disease evol ution 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 th e prevention of disease progression.