A viral long terminal repeat in the interleukin 2 gene of a cell line that constitutively produces interleukin 2

Abstract

The gibbon leukemia cell line MLA 144 differs from every other T-lymphocyte line in that it constitutively makes interleukin 2 (IL-2) (also called T-cell growth factor) without stimulation by antigen, lectin, or tumor promoters. Previous work in which glucocorticoids were used to inhibit IL-2 production has indicated that proliferation of this cell line is dependent upon endogenously produced IL-2. We have found that the MLA 144 cell line has a copy of the gibbon leukemia virus inserted into the 3' nontranslated region of the IL-2 gene. This integration event produces a composite mRNA made up of the protein coding sequences of the IL-2 gene transcript but incorporating the viral long terminal repeat (LTR) in the 3' nontranslated region of the mRNA. This composite mRNA transcript uses the polyadenylylation signal in the viral 5' LTR and incorporates the viral transcriptional control regions. The integration event must involve only one allele of the IL-2 gene, since transcripts essentially identical to normal human IL-2 mRNA are also produced in cloned sublines of MLA 144. That the viral LTR contains a 94-base-pair repeat reminiscent of enhancer sequences in several viruses suggests that the integration of the viral LTR at the 3' end of the IL-2 gene is responsible for the constitutive production of IL-2 in the MLA 144 cell line.