Antigen-driven long term-cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy, and persist long-term as functional memory T cells.
Mice bearing disseminated syngeneic FBL-3 leukemia were treated with cyclophosphamide plus long term-cultured T cells immune to FBL-3. The cultured T cells for therapy had been induced to grow in vitro for 62 d by intermittent stimulation with irradiated FBL-3. At the time of therapy, such antigen-driven long term-cultured T cells were greatly expanded in number, proliferated in vitro in response to FBL-3, and were specifically cytotoxic. Following adoptive transfer, donor T cells persisting in the host were identified and counted using donor and host mice congenic for the T cell marker Thy-1. The results show that antigen-driven long term-cultured T cells proliferated rapidly in vivo, distributed widely in host lymphoid organs, and were effective in tumor therapy. Moreover, the already rapid in vivo growth rate of donor T cells could be augmented by administration of exogenous IL-2. When cured mice were examined 120 d after therapy, donor L3T4+ T cells and donor Lyt-2+ T cells could be found in large numbers in host ascites, spleen, and mesenteric and axillary lymph nodes. The persisting donor T cells proliferated in vitro, and became specifically cytotoxic in response to FBL-3, demonstrating that antigen-driven long term-cultured T cells can persist long term in vivo and provide immunologic memory.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D002453:Cell Cycle; D002470:Cell Survival; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D007116:Immunization, Passive; D007156:Immunologic Memory; D007167:Immunotherapy; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000628:therapy; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014018:Tissue Distribution
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D003520:Cyclophosphamide