Quantitation and clonal isolation of cytolytic T lymphocyte precursors selectively infiltrating murine sarcoma virus-induced tumors.
A limiting dilution mixed leukocyte-tumor cell microculture system was used to quantitate cytolytic T lymphocytes and their precursors (CTL-P), which infiltrate tumors induced by injection of Moloney sarcoma-leukemia virus (MSV-MoLV) complex into C57BL/6 mice. Leukocyte populations obtained from tumors collected on day 10 after virus injection were found to contain significantly higher frequencies of operationally defined (tumor-specific) CTL-P than either peripheral blood leukocytes (PBL) or spleen cells from the same animals. When these frequencies were normalized according to the content of Lyt-2+ T cells in each tissue, average CTL-P frequencies were found to be 1/9 in tumor-infiltrating cells vs. 1/41 in PBL. These results directly demonstrate selective accumulation of CTL-P in the tumor mass. A number of clonal isolates obtained from tumor-infiltrating leukocyte populations were expanded and studied for cytolytic activity and specificity. Of 11 isolates, 10 were found to have high cytolytic activity, leading to 50% lysis of the syngeneic MoLV-derived tumor target cells in 3.5 h at lymphocyte:target cell ratios ranging from 0.5:1 to 3.2:1. Furthermore, five randomly selected clones showed H-2 restriction by their selective lytic activity against MoLV-derived syngeneic MBL-2 target cells and their lack of activity against either MoLV-derived allogeneic (LSTRA) tumor cells or against syngeneic (EL4) or allogeneic (P815) target cells unrelated to MoLV.
D000818:Animals; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D007942:Leukemia, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology; D008979:Moloney murine leukemia virus / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*