INACTIVATED INFLUENZA-VIRUS, WHEN PRESENTED ON DENDRITIC CELLS, ELICITS HUMAN CD8(-CELL RESPONSES() CYTOLYTIC T)

Inactivated or subunit virus preparations have been excellent vaccines for inducing antibody responses. Generation of cytolytic T cell respo nses, however, is thought to require replicating virus, primarily to p rovide sufficiently large amounts of cytoplasmic proteins for processi ng and presentation on major histocompatibility complex class I molecu les by antigen-presenting cells. Potent human CD8(+) cytolytic T cell responses to live replicating influenza A virus are generated when den dritic cells are used as the antigen-presenting cells. Here, we demons trate that dendritic cells pulsed with poorly replicating, heat- or ul traviolet-inactivated influenza virus, induce equally strong CD8(+) cy tolytic T lymphocyte responses. The cytotoxic T lymphocytes are genera ted in the apparent absence of CD4(+) helper cells or exogenous cytoki nes. Active viral protein synthesis is not required to charge class I molecules on dendritic cells. When pulsed with inactivated virus, <1% of dendritic cells express nonstructural protein 1, which is only synt hesized in the infectious cycle. To be optimally effective, however, t he inactivated virus must retain its fusogenic activity, and presumabl y access the cytoplasm of dendritic cells. The data indicate, therefor e, that dendritic cells require only small amounts of viral protein to charge class I molecules, most likely via traditional class I process ing pathways. These results reopen the potential use of inactivated vi rus preparations as immunogens for cytotoxic T lymphocyte responses.