Dual function of Drosophila cells as APCs for naive CD8+ T cells: implications for tumor immunotherapy.
With unseparated mouse spleen cells as responders, Drosophila cells expressing MHC class I (L(d)) molecules alone lead to peptide-specific responses of CD8+ cells in the absence of exogenous cytokines. Under these conditions, DNA released from dying cells stimulates the B cells in spleen to up-regulate costimulatory molecules; these activated B cells then provide bystander costimulation for CD8+ cells responding to class I-peptide complexes on the Drosophila APCs. By stimulating B cells and presenting antigen to T cells, Drosophila cells thus serve two different functions in promoting primary responses of CD8+ cells in vitro. With this system, we show that Ld-transfected Drosophila cells are able to induce autologous spleen cells to respond to a tumor-specific peptide in vitro and, after transfer, cause tumor rejection in vivo.
Sun
S
S
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Cai
Z
Z
Langlade-Demoyen
P
P
Kosaka
H
H
Brunmark
A
A
Jackson
M R
MR
Peterson
P A
PA
Sprent
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology / Q000494:pharmacology; D004330:Drosophila / Q000166:cytology / Q000235:genetics / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008934:Mitogens / Q000494:pharmacology; D013154:Spleen / Q000276:immunology
D008934:Mitogens; D004247:DNA