Tumor-specific T cell lines: capacity to proliferate and produce interleukin 2 in response to various forms of tumor antigens.
Anti-tumor proliferative T cell lines were established from cultures of lymph node cells from BALB/c mice immunized to syngeneic CSA1M fibrosarcoma with the CSA1M tumor cell membrane. The cultures were maintained throughout in the absence of exogenous interleukin 2 (IL2). Cell surface phenotypes of all T cell lines established were Thy-1+, Ig-, L3T4+ and Lyt-2-. Their proliferation was induced in a tumor antigen dose-dependent fashion and a tumor antigen-specific way. Such proliferative responses were inhibited by the addition to cultures of anti-class II H-2d (anti-I-Ad) or anti-L3T4 but not of anti-class I H-2d or anti-Lyt-2 monoclonal antibody. None of the T cell lines exhibited any cytotoxic T lymphocyte activity but they all produced IL2 upon stimulation with CSA1M tumor antigens, indicating that they represent helper-type T cell (Th) lines. The activation of these tumor-specific Th lines was induced with either CSA1M tumor cells themselves, or their membrane or detergent-solubilized fraction depending on the presence of antigen-presenting cells (APC). Most importantly, activation was also inducible by membranous tumor antigen-pulsed APC, which were capable of producing potent anti-tumor protective immunity when administered in vivo into syngeneic BALB/c mice. These results indicate that the tumor-specific Th lines established here can be activated with various forms of tumor antigens for their expression of helper function. Since Th lines of this type have not been described previously, our Th lines provide an intriguing tool for investigating the cellular and molecular mechanisms by which tumor-specific Th recognize tumor antigens.
Shimizu
J
J
Biomedical Research Center, Osaka University Medical School.
Suda
T
T
Katagiri
T
T
Fujiwara
H
H
Hamaoka
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes