PRIMING OF TUMOR-SPECIFIC T-CELLS IN THE DRAINING LYMPH-NODES AFTER IMMUNIZATION WITH INTERLEUKIN 2-SECRETING TUMOR-CELLS - 3 CONSECUTIVE STAGES MAY BE REQUIRED FOR SUCCESSFUL TUMOR VACCINATION

Although both CD4(+) and CD8(+) T cells are clearly required to genera te long-lasting anti-tumor immunity induced by s.c. vaccination with i nterleukin 2 (IL-2)-transfected, irradiated M-3 clone murine melanoma cells, some controversy continues about the site and mode of T-cell ac tivation in this system, Macrophages, granulocytes, and natural killer cells infiltrate the vaccination site early after injection into eith er syngeneic euthymic DBA/2, mice or athymic nude mice and eliminate t he 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, re verse transcription-PCR revealed transcripts indicative of T-cell acti vation and expansion in the draining lymph nodes of mice immunized wit h the IL-2-secreting vaccine but not in mice vaccinated with untransfe cted, irradiated M-3 cells, We therefore propose that the antigen-pres enting cells, which invade the vaccination site, process tumor-derived antigens and, subsequently, initiate priming of tumor-specific T lymp hocytes in lymphoid organs, These findings suggest a three-stage proce ss 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 antig en-presenting cells into the regional draining lymph nodes, where T-ce ll priming occurs, and (iii) circulation of activated T cells that eit her perform or initiate effector mechanisms leading to tumor cell dest ruction.