       Document 0343
 DOCN  M9630343
 TI    Inactivated influenza virus, when presented on dendritic cells, elicits
       human CD8+ cytolytic T cell responses.
 DT    9603
 AU    Bender A; Bui LK; Feldman MA; Larsson M; Bhardwaj N; Rockefeller
       University, Laboratory of Cellular Physiology and; Immunology, New York
       10021, USA.
 SO    J Exp Med. 1995 Dec 1;182(6):1663-71. Unique Identifier : AIDSLINE
       MED/96096440
 AB    Inactivated or subunit virus preparations 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.
 DE    Antigen-Presenting Cells/*IMMUNOLOGY  Antigens, Viral/*IMMUNOLOGY
       Cells, Cultured  *Cytotoxicity, Immunologic  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/*IMMUNOLOGY
       Dendritic Cells/*IMMUNOLOGY  Histocompatibility Antigens Class
       I/IMMUNOLOGY  Human  Influenza Vaccine/*IMMUNOLOGY
       Orthomyxoviridae/*IMMUNOLOGY  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Vaccines, Attenuated/IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

