Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
INTERLEUKIN 2 RECEPTOR INDUCERS: PATHOLOGICAL ROLES IN ADULT T CELL LEUKEMIA
Interleukin 2. Smith KA, ed. New York, Academic, p. 197-222, 1988.. Unique Identifier : AIDSLINE ICDB/89656589 Yodoi J; Tagaya Y; Maeda M; Inst. for Immunology, Faculty of Medicine, Kyoto Univ., Yoshida,; Sakyo-ku, Kyoto 606, Japan
Abstract:
The functional state and expression of hormone and cytokine receptors are regulated by the specific ligands for the respective receptors and by unrelated mediators. Such a regulatory circuit in the interleukin 2 (IL-2)/IL-2 receptor (IL-2R) system is discussed and its key role in the immune system relative to T-cell leukemogenesis by human T-lymphotropic virus (HTLV)-I is considered. Topics include studies of IL-2R and adult T-cell leukemia (ATL), properties of human IL-2R protein, cloning of IL-2R gene, humoral control of IL-2R expression, abnormal regulation of IL-2R expression in ATL, ATL-derived factor (ADF) inducing IL-2R expression, a stepwise progression model of IL-2-dependent and -independent ATL, and possible roles of IL-2R dysregulation in ATL. HTLV-I+ leukemic T cells and T-cell lines from patients with ATL continuously expressed IL-2R without significant production of IL-2. The lack of downregulation of IL-2R by anti-Tac monoclonal antibody recognizing IL-2R suggested the presence of an abnormality in the IL-2R system in ATL, but there was no aberration in the size and charge of Tac antigen unique to ATL. The cDNA coding for Tac antigen also coded for IL-2R, proving that Tac epitope is expressed on the IL-2R molecule. In ATL cell lines and in fresh leukemic cells of ATL, however, there was no abnormality of the structural gene for IL-2R, despite the continued elevation of mRNA for IL-2R. Many HTLV-I+ T4+ T-cell lines constitutively produce the non-IL-2 lymphokine ADF, which induced the expression of the high-affinity IL-2R on a variety of cells, including HTLV-I+ T cells and the HTLV-I- natural-killer-like leukemic cell line cells (YT cells). Expression of IL-2R on YT cells as induced by a variety of agents, including ADF, IL-1s, phorbol esters, and forskolin which is a direct activator of adenylate cyclase, but not by T-cell mitogens or IL-2. Purified ADF has a mol wt of about 13,000-17,000 on gel filtration and 15,000-20,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and is an acid protein with a pI of 4.5-5.5. ADF activates expression of IL-2R and its gene by enhancing the transcription of IL-2R mRNA. There are functional antigenic differences between ADF and other IL-2R-inducing cytokines such as IL-1s. Constitutively expressed IL-2R in leukemogenesis actually may be involved in the neoplastic growth of ATL cells or the IL-2R on ATL cells may play a key role in leukemogenesis, but not be involved in the continued proliferation of leukemic cells. (74 Refs)
Keywords: Animal Cell Line Cloning, Molecular Gene Expression Regulation Human Interleukin-2/GENETICS/*PHYSIOLOGY Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/GENETICS/ PHYSIOPATHOLOGY Leukemia, T-Cell/GENETICS/*PHYSIOPATHOLOGY Ligands Lymphokines/PHYSIOLOGY Models, Biological Neoplasm Proteins/GENETICS/PHYSIOLOGY Receptors, Interleukin-2/DRUG EFFECTS/GENETICS/*PHYSIOLOGY MONOGRAPH REVIEW REVIEW, TUTORIAL
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Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
