Dendritic cells incubated with irradiated tumor cells effectively stimulate T lymphocyte activation and induce enhanced expression of CD69, CD25 as well as production of IFNgamma and IL4.
Understanding of immunological processes at the molecular level in the cancer-bearing organism is the prerequisite for development of specific tumor vaccines. Most of these vaccines are aimed at enhancing the immunogenicity of the antigens presented by the tumor cells. Since dendritic cells (DC) are potent antigen presenting cells (APC) in the organism, they are considered as a powerful tool to deliver the signals essential for the activation of immune system. In an attempt to clarify the functional importance of DC in the process of anti-tumor vaccination, we characterized the effect of DC activated with a classical tumor vaccine (mixture of irradiated B16F1 tumor cells and MVE-2) on the activation of T lymphocytes. The T lymphocyte activation was assessed by determination of expression of CD25, CD69, and intracellular IFNgamma and IL4 production. Activated DC significantly increased the proportion of CD25+ and CD69+ cells as well as IFNgamma+ and IL4+ cells among CD3+ T lymphocytes. On the other hand, the direct effect of the tumor vaccine on T lymphocytes was just an increment in the proportion of IL4+ T lymphocytes. With the results of in vivo experiments, the phagocytic cells (including DC) were proved to be essential for establishing an active protection against tumor cells (tumor development), but more importantly, also for formation of the memory cell pool. These data indicate that DC loaded with tumor antigens are required for effective stimulation of T lymphocytes, and that the phagocytic cells (including DC) are essential for the anti-tumor immunity triggered by this kind of vaccine.
Stegel
Vida
V
Department of Tumor Biology, Institute of Oncology, Zaloska 2, 1000 Ljubljana, Slovenia.
Kopitar
Andreja
A
Jezersek Novaković
Barbara
B
Ihan
Alojz
A
Novaković
Srdjan
S
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D007371:Interferon-gamma; D015847:Interleukin-4; D037181:Lectins, C-Type; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens