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M9640683.TXT
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1996-03-04
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Document 0683
DOCN M9640683
TI Murine dendritic cells loaded in vitro with soluble protein prime
cytotoxic T lymphocytes against tumor antigen in vivo [see comments]
DT 9604
AU Paglia P; Chiodoni C; Rodolfo M; Colombo MP; Division of Experimental
Oncology D, Istituto Nazionale per lo; Studio e la Cura dei Tumori,
Milano, Italy.
SO J Exp Med. 1996 Jan 1;183(1):317-22. Unique Identifier : AIDSLINE
MED/96136777
CM Comment in: J Exp Med 1996 Jan 1;183(1):7-11
AB The priming of an immune response against a major histocompatibility
complex class I-restricted antigen expressed by nonhematopoietic cells
involves the transfer of that antigen to a host bone marrow-derived
antigen presenting cell (APC) for presentation to CD8+ T lymphocytes.
Dendritic cells (DC), as bone marrow-derived APC, are first candidates
for presentation of tumor-associated antigens (TAA). The aim of this
study was to see whether DC are able to prime in vivo antigen-specific
cytotoxic T lymphocytes after exposure to a soluble protein antigen in
vitro. Lacking a well-defined murine TAA, we took advantage of
beta-galactosidase (beta-gal)-transduced tumor cell lines as a model in
which beta-gal operationally functions as TAA. For in vivo priming both
a DC line, transduced or not transduced with the gene coding for murine
GM-CSF, and fresh bone marrow-derived DC (bm-DC), loaded in vitro with
soluble beta-gal, were used. Priming with either granulocyte macrophage
colony-stimulating factor-transduced DC line or fresh bm-DC but not with
untransduced DC line generated CTL able to lyse beta-gal-transfected
target cells. Furthermore, GM-CSF was necessary for the DC line to
efficiently present soluble beta-gal as an H-2Ld-restricted peptide to a
beta-gal-specific CTL clone. Data also show that a long-lasting immunity
against tumor challenge can be induced using beta-gal-pulsed bm-DC as
vaccine. These results indicate that effector cells can be recruited and
activated in vivo by antigen-pulsed DC, providing an efficient immune
reaction against tumors.
DE beta-Galactosidase/IMMUNOLOGY Animal Bone Marrow/CYTOLOGY/IMMUNOLOGY
Clone Cells/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Dendritic
Cells/*IMMUNOLOGY Female Histocompatibility Antigens Class
I/IMMUNOLOGY Immunization Schedule Lymphocyte Transformation Mice
Mice, Inbred BALB C Neoplasms, Experimental/*THERAPY Peptide
Fragments/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't,
Non-P.H.S. T-Lymphocytes, Cytotoxic/*IMMUNOLOGY *Vaccination
Vaccines/IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).