IL-2 receptor gene regulation by cytokines; Role of ATL-derived factor(s) (ADFs) in ATL

Junji Yodoi, Yutaka Tagaya, Masafumi Okada, Masakazu Hirata, Tsunehisa Namba, Mayumi Naramura

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Abstract

The humoral regulation of the IL-2 receptor (IL-2-R) gene expression was studied on the transcriptional as well as post-transcriptional levels. HTLVI (+) leukemic T-cells and T-cell lines from the patients with Adult T-cell Leukemia (ATL) continuously expressed IL-2-R without production o£ IL-2. However, there was no abnormality of the structural gene for the IL-2-R in these cell lines as well as fresh leukemic cells o£ ATL. We have detected that many HTLV-I (+) T4(+) T-cell lines constitutively produce a non-IL-2 lymphokine named ATL-derived factor (ADF), which induced the expression of the high affinity IL-2-R on a variety of the cells including HTLV-I(+) T-cells as well as YT cells, a sensitive human NK cell line without rearrangement of T beta gene. IL-2-R on YT cells was also induced by a variety of IL-1s but not by IL-2, which effectively induced IL-2-R on T-cell lines. IL-2-R gene expression on YT cells is also induced by a variety of pharmacological agents including phorbol esters such as phorbol myristate acetate (PMA) and Forskolin, a direct activator of adenylate cyclase. In contrast to the preferential induction of the low affinity IL-2-R by PMA, Forskolin induced the high affinity IL-2-R on YT cells. These IL-2-R inducing agents such as ADF and Forskolin were shown to induce the elevation of the levels of mRNA for IL-2-R, through the enhancement of the transcription of the IL-2-R gene. The possible involvement of IL-2-R inducing cytokines in the physiological lymphocyte activation and the malignant transformation in ATL and other T-cell leukemias is discussed.

Original languageEnglish (US)
Pages (from-to)719-734
Number of pages16
JournalACTA HISTOCHEMICA ET CYTOCHEMICA
Volume19
Issue number6
DOIs
Publication statusPublished - Jan 1 1986

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Biochemistry
  • Physiology
  • Histology
  • Cell Biology

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