Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination.
Although both CD4+ and CD8+ T cells are clearly required to generate long-lasting anti-tumor immunity induced by s.c. vaccination with interleukin 2 (IL-2)-transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell activation in this system. Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into either syngeneic euthymic DBA/2 mice or athymic nude mice and eliminate the inoculum within 48 hr. We could not find T cells at the vaccination site, which argues against the concept that T-cell priming by the IL-2-secreting cancer cells occurs directly at that location. However, reverse transcription-PCR revealed transcripts indicative of T-cell activation and expansion in the draining lymph nodes of mice immunized with the IL-2-secreting vaccine but not in mice vaccinated with untransfected, irradiated M-3 cells. We therefore propose that the antigen-presenting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor-specific T lymphocytes in lymphoid organs. These findings suggest a three-stage process for the generation of effector T cells after vaccination with IL-2-secreting tumor cells: (i) tumor-antigen uptake and processing at the site of injection by antigen-presenting cells, (ii) migration of antigen-presenting cells into the regional draining lymph nodes, where T-cell priming occurs, and (iii) circulation of activated T cells that either perform or initiate effector mechanisms leading to tumor cell destruction.
Maass
G
G
Research Institute of Molecular Pathology, Vienna, Austria.
Schmidt
W
W
Berger
M
M
Schilcher
F
F
Koszik
F
F
Schneeberger
A
A
Stingl
G
G
Birnstiel
M L
ML
Schweighoffer
T
T
D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D007376:Interleukin-2 / Q000378:metabolism* / Q000627:therapeutic use; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000648:ultrastructure; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
D016207:Cytokines; D017931:DNA Primers; D007376:Interleukin-2; D012333:RNA, Messenger; D014612:Vaccines