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.
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.
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M A Cheever, D B Thompson, J P Klarnet, P D Greenberg; 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.. J Exp Med 1 May 1986; 163 (5): 1100–1112. doi: https://doi.org/10.1084/jem.163.5.1100
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