JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathy.
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.
Du Pasquier
R A
RA
Department of Neurology and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Clark
K W
KW
Smith
P S
PS
Joseph
J T
JT
Mazullo
J M
JM
De Girolami
U
U
Letvin
N L
NL
Koralnik
I J
IJ
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