Generation of cytotoxic T lymphocytes specific for human cytomegalovirus using dendritic cells in vitro

For the adoptive immunotherapy in immunodeficient bone marrow transplant re cipients to prevent and treat human cytomegalovirus (HCMV)-associated disea ses, HCMV-pulsed dendritic cells (DCs) were used as antigen-presenting cell s for the induction of cytotoxic T lymphocytes (CTLs) specific to HCMV anti gens in vitro. The antiviral CTL responses induced by HCMV-pulsed DCs were as highly efficient as those induced by HCMV-infected dermal fibroblasts, a nd endogenous viral gene expression was not required to induce virus-specif ic T-cell lines. The strong cytotoxic activity against HCMV-pp65, known as HCMV major antigen, was identified using autologous B lymphoblastoid cell l ine expressing pp65 antigen. The cytotoxic activity toward HCMV-infected ta rget cells was found to be mediated primarily by CD8(+) T cells, although b oth CD8(+) cells and CD4(+) cells were able to lyse autologous virus-infect ed target cells. The CTLs contained a mixture of effector cells that recogn ized virus peptides in the context of major histocompatibility complex. Thi s system may be useful for defining the cellular immune response to HCMV an d for the treatment of HCMV infection in immunocompromised patients.