Immune Reconstitution after Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Selective Control of JC Virus Reactivation

JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. The mechanism of JCV reactivation and immunity in a transplanted immune system remains unclear. We prospectively studied 30 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) and collected blood and urine samples before HSCT and 3, 6, and 12 to 18 months after HSCT. Before HSCT, JCV DNA was detected in 7 of 30 urine, 5 of 30 peripheral blood mononuclear cells (PBMC) and 6 of 30 plasma samples. Although JC viruria remained stable after HSCT with detection in 5 of 21 samples, viremia was detected in only 1 of 22 plasma and none of 22 PBMC samples 12 to 18 months after HSCT. Prevalence of anti-JCV IgG was 83% before HSCT and decreased to 72% at 12 to 18 months. Anti-JCV IgM was rarely detected. JCV-specific CD4+ and CD8+ T cell responses increased 12 to 18 months after HSCT. Although JC viruria correlated directly with detection of anti-JCV IgG, the cellular immune response to JCV measured by ELISpot was inversely correlated with anti-JCV IgG response. The diagnosis of acute myelogenous leukemia and age group were 2 independent patient factors associated with significantly reduced cellular immune responses to JCV. This prospective study in HSCT patients provides a model of interactions between the host immune response and viral activation in multiple compartments during the recovery of the immune system.