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 (Thy1.2, Lyt1.2) 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 (greater than 3 months) can undergo transformation and, therefore, should not be utilized for immunotherapeutic purposes.
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology; D007621:Karyotyping; D008745:Methylation; D051379:Mice; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D004273:DNA, Neoplasm; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2