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Updated: Oct 24, 2026

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
Published on: December 7, 2019
T-cell turnover in vivo and the role of cytokines
1Department of Immunology, IMM4, The Scripps Research Institute, La Jolla CA 92037, USA. jsprent@scripps.edu
In addition to responding to specific antigen, CD8+ T-cells with a memory (CD44hi) phenotype undergo bystander proliferation when exposed to certain cytokines, notably type I interferons (IFN I), in vivo; such proliferation does not require T-cell receptor ligation. Since IFN I is unable to induce proliferation of purified CD44hi CD8+ cells in vitro, stimulation of these cells in vivo may reflect IFN I-dependent release of other cytokines. Evidence is presented that IFN I induces macrophages to synthesize IL-15 mRNA and that, at the protein level, IL-15 causes selective stimulation of CD44hi CD8+ (but not CD4+) cells, both in vitro and in vivo. This finding raises the possibility that synthesis of IL-15 during infection may induce bystander proliferation of memory-phenotype CD8+ cells.
In addition to responding to specific antigen, CD8+ T-cells with a memory (CD44hi) phenotype undergo bystander proliferation when exposed to certain cytokines, notably type I interferons (IFN I), in vivo; such proliferation does not require T-cell receptor ligation. Since IFN I is unable to induce proliferation of purified CD44hi CD8+ cells in vitro, stimulation of these cells in vivo may reflect IFN I-dependent release of other cytokines. Evidence is presented that IFN I induces macrophages to synthesize IL-15 mRNA and that, at the protein level, IL-15 causes selective stimulation of CD44hi CD8+ (but not CD4+) cells, both in vitro and in vivo. This finding raises the possibility that synthesis of IL-15 during infection may induce bystander proliferation of memory-phenotype CD8+ cells.
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