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1996-02-27
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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).