Inactivated influenza virus, when presented on dendritic cells, elicits human CD8+ cytolytic T cell responses

Armin Bender, Long Kim Bui, Mary A.V. Feldman, Marie Larsson, Nina Bhardwaj

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Inactivated or subunit virus preparation have been excellent vaccines for inducing antibody responses. Generation of cytolytic T cell responses, however, is thought to require replicating virus, primarily to provide sufficiently large amounts of cytoplasmic proteins for processing and presentation on major histocompatibility complex class I molecules by antigen-presenting cells. Potent human CD8+ cytolytic T cell responses to live replicating influenza A virus are generated when dendritic cells are used as the antigen-presenting cells. Here, we demonstrate that dendritic cells pulsed with poorly replicating, heat- or ultraviolet-inactivated influenza virus, induce equally strong CD8+ cytolytic T lymphocyte responses. The cytotoxic T lymphocytes are generated in the apparent absence of CD4+ helper cells or exogenous cytokines. 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 synthesized in the infectious cycle. To be optimally effective, however, the inactivated virus must retain its fusogenic activity, and presumably access the cytoplasm of dendritic cells. The data indicate, therefore, that dendritic cells require only small amounts of viral protein to charge class I molecules, most likely via traditional class I processing pathways. These results reopen the potential use of inactivated virus preparations as immunogens for cytotoxic T lymphocyte responses.

Original languageEnglish
Pages (from-to)1663-1671
Number of pages9
JournalJournal of Experimental Medicine
Volume182
Issue number6
DOIs
StatePublished - 1 Dec 1995
Externally publishedYes

Fingerprint

Dive into the research topics of 'Inactivated influenza virus, when presented on dendritic cells, elicits human CD8+ cytolytic T cell responses'. Together they form a unique fingerprint.

Cite this