Characterization of a tumorigenic murine T‐lymphoid‐cell line spontaneously derived from an IL‐2‐dependent T‐cell line

The establishment of IL‐2‐independent T‐cell lines spontaneously derived from long‐term IL‐2‐dependent cytotoxic T‐cell lines is described. Two lines (cloned and uncloned) studied in detail have shown the following characteristics: (1) Permanent loss of IL‐2 dependence. (2) Partial or complete loss of both cytotoxic activity and the IL‐2 receptor. (3) Increased expression of T‐cell membrane markers (Thy 1.2, Lyt 1.2) compared with the parental line. (4) Lower level of DNA methylation than in freshly obtained lymphoid cells. (5) Different karyotypic pattern from the parental IL‐2‐dependent line, with a mean number of 39–40 chromosomes and a resemblance to T leukemic lines. (6) Leukemia caused in normal syngeneic C57BL/6 mice by the uncloned line, in contrast to the cloned IL‐2‐independent line or the parental dependent line. Unlike established leukemic lines, however, the independent line gave rise to tumors which regressed in some mice within a few days of their appearance. These findings suggest that T‐cell lines maintained with IL‐2 for prolonged periods of time (> 3 months) can undergo transformation and, therefore, should not be utilized for immunotherapeutic purposes.