Helper T cells against tumor-associated antigens (TAA): preferential induction of helper T cell activities involved in anti-TAA cytotoxic T lymphocyte and antibody responses.
This study establishes assay systems for helper T cell activities assisting cytotoxic T lymphocyte (CTL) and antibody responses to tumor-associated antigens (TAA) and demonstrates the existence of TAA that induce preferentially anti-TAA CTL helper and B cell helper T cell activities in two syngeneic tumor models. C3H/HeN mice were immunized to the syngeneic X5563 plasmacytoma or MH134 hepatoma. Spleen cells from these mice were tested for anti-TAA helper T cell activity capable of augmenting anti-trinitrophenyl(TNP) CTL and anti-TNP antibody responses from anti-TNP CTL and B cell precursors (responding cells) by stimulation with TNP-modified X5563 or MH134 tumor cells. The results demonstrate that cultures of responding cells plus 85OR X-irradiated tumor-immunized spleen cells (helper cells) failed to enhance anti-TNP CTL or antibody responses when in vitro stimulation was provided by either unmodified tumor cells or TNP-modified syngeneic spleen cells (TNP-self). In contrast, these cultures resulted in appreciable augmentation of anti-TNP CTL or antibody response when stimulated by TNP-modified tumor cells. Such anti-TAA helper activities were revealed to be Lyt-1+2- T cell mediated and TAA specific. Most interestingly, immunization with X5563 tumor cells resulted in anti-TAA helper T cell activity involved in CTL, but not in antibody responses. Conversely, TAA of MH134 tumor cells induced selective generation of anti-TAA helper T cell activity responsible for antibody response. These results indicate that there exists the qualitative TAA-heterogeneity as evidenced by the preferential induction of anti-TAA CTL- and B cell-helper T cell activities. The results are discussed in the light of cellular mechanisms underlying the preferential anti-TAA immune responses, and the interrelationship between various types of cell functions including CTL- and B cell-help.
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis; D015847:Interleukin-4; D008113:Liver Neoplasms / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis; D051379:Mice; D008809:Mice, Inbred C3H; D010954:Plasmacytoma / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D006133:Growth Substances; D008222:Lymphokines; D015847:Interleukin-4