A human Langerhans cell-like cell line, ELD-1, promotes CD8 T cells to produce IFN-gamma through CD70-dependent alternative pathway.
A novel pathway of CD8+ T-cell activation by a previously established human Langerhans cell (LC)-like cell line, ELD-1 [Dendritic Cells 9 (1999) 41] is reported. ELD-1 cells possess LC-specific and dendritic cell (DC) lineage-specific markers including Birbeck granules. Intriguingly, ELD-1 cells stimulated interferon (IFN)-gamma production by purified allogeneic CD8+ T cells in an IL-2- but not IL-12-dependent manner, but failed to stimulate CD4+ T cells due to their lack of HLA-DR, CD40, CD80, and CD86 expression. Comparing active and inactive subclones of ELD-1 cells revealed that CD70 was a key molecule determining stimulatory ability. This was confirmed by the ability of transfected CD70-encoding cDNA to confer stimulatory capacity on inactive subclones of ELD-1. Therefore, it is concluded that CD70 expressed on ELD-1 cells has a crucial role in stimulating IFN-gamma production by CD8+ T cells through an alternative pathway which does not require CD4+ T-cell help or CD28-B7 interactions.
Iwamoto
Sanju
S
Department of Biochemistry, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan. iwasanju@med.showa-u.ac.jp
Ishida
Makoto
M
Tamaoki
Satoshi
S
Hagiwara
Tamio
T
Sueki
Hirohiko
H
Miyazaki
Akira
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D053282:CD27 Ligand; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D018076:DNA, Complementary / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D010641:Phenotype; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D018076:DNA, Complementary; D008565:Membrane Proteins; D007371:Interferon-gamma