Interleukin 2-dependent activation of tumor-specific cytotoxic T lymphocytes in vivo.
We have quantitatively studied the effect of interleukin (IL) 2 on the cytotoxic T lymphocyte (CTL) response to tumor cells in vivo. Mastocytoma P815 was transfected with murine IL 2 cDNA (P815-IL 2) and injected into syngeneic mice. The anti-tumor response was analyzed and compared with the response induced by the non-transfected cells. P815 parental cells are highly tumorigenic, causing death within 20-30 days. In contrast, IL 2-transfected cells were totally rejected. Co-injection of IL 2-secreting and parental cells resulted in the inhibition of growth of both type of tumors. In addition, the response induced by IL 2-secreting cells protected the mice against a subsequent challenge with P815. Long-term memory persisted in treated mice 3 months after tumor rejection. Frequencies of CTL precursors and CTL specific for P815 increased as a result of IL 2 secretion by the target cells. Estimates of CTL frequency at days 8 and 12 after injection were 2 to 3 times higher in mice inoculated with P815-IL 2 cells, and this correlated with tumor rejection.
Ley
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Unité de Biologie Moléculaire du Gène, U.277 INSERM, U.A.C. 535 CNRS, Institut Pasteur, Paris, France.
Langlade-Demoyen
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Kourilsky
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Larsson-Sciard
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D000818:Animals; D003602:Cytotoxicity, Immunologic; D006410:Hematopoiesis; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000276:immunology*; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D007376:Interleukin-2; D011994:Recombinant Proteins