Interleukin-15 (IL-15) can replace the IL-2 signal in IL-2-dependent adult T-cell leukemia (ATL) cell lines: expression of IL-15 receptor alpha on ATL cells.

Interleukin-15 receptor (IL-15R) and IL-2R have the same beta and gamma chains, but IL-15R has a specific alpha chain distinct from that of IL-2Ralpha, which is indispensable for the high affinity binding of IL-15. In the present study, we examined four IL-2-dependent adult T-cell leukemia (ATL) cell lines for their IL-15R expression. All cell lines bound IL-15, which was not inhibited by a 100-fold excess amount of IL-2, proliferated in response to IL-15 to the same degree as to the stimulation with IL-2, and were maintained without IL-2. The responses to 1L-15 were inhibited by the antibodies against IL-2R beta or gamma chains but was not by the IL-2R alpha chain antibody. [125I]-IL-15 exhibited a single high-affinity binding with an apparent kd of 0.17 nmol/L. Reverse transcription-coupled polymerase chain reaction (RT-PCR) showed that the cell lines had the mRNA of IL-15R alpha. The cell lines also had IL-15 mRNA. Despite the presence of IL-15 mRNA, the cell lines did not secrete IL-15, and the culture supernatants of fresh ATL cells and plasma from the patients did not contain a detectable amount of IL-15 with a few exceptional cases, although fresh ATL cells also responded to IL-15. These results suggest that ATL cells have the complete form of IL-15R and respond to IL-15. Such an IL-15-dependent cell proliferation mechanism might be used in the development of ATL and for the invasion and proliferation of ATL cells in the visceral organs.

[1]  M. Tomonaga,et al.  Frequent hepatic involvement in adult T cell leukemia: comparison with non-Hodgkin's lymphoma. , 1997, Leukemia & lymphoma.

[2]  河野友子.  Relation of Oxidative Stress and Glutathione Synthesis to CD95(Fas/APO-1)-Mediated Apoptosis of Adult T Cell Leukemia Cells , 1997 .

[3]  T. Pohl,et al.  Regulation of IL-15 secretion via the leader peptide of two IL-15 isoforms. , 1997, Journal of immunology.

[4]  F Rodeghiero,et al.  Interleukin-15 triggers the proliferation and cytotoxicity of granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes. , 1997, Blood.

[5]  I. Puzanov,et al.  IL-15 can substitute for the marrow microenvironment in the differentiation of natural killer cells. , 1996, Journal of immunology.

[6]  A. Beaulieu,et al.  Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15. , 1996, Blood.

[7]  D. Anderson,et al.  Expression of interleukin-15 and its receptor by human fetal retinal pigment epithelial cells. , 1996, Current eye research.

[8]  G. Leclercq,et al.  Differential effects of interleukin-15 and interleukin-2 on differentiation of bipotential T/natural killer progenitor cells , 1996, The Journal of experimental medicine.

[9]  D. Cosman,et al.  Interleukin‐15 up‐regulates interleukin‐2 receptor α chain but down‐regulates its own high‐affinity binding sites on human T and B cells , 1996, European journal of immunology.

[10]  F. Rodeghiero,et al.  Interleukin-15 promotes the growth of leukemic cells of patients with B-cell chronic lymphoproliferative disorders. , 1996, Blood.

[11]  T. Waldmann,et al.  Interleukin (IL) 15/IL-T production by the adult T-cell leukemia cell line HuT-102 is associated with a human T-cell lymphotrophic virus type I region /IL-15 fusion message that lacks many upstream AUGs that normally attenuates IL-15 mRNA translation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  T. Waldmann,et al.  IL-15: a pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels. , 1996, Immunity.

[13]  T. Waldmann,et al.  IL‐15: the role of translational regulation in their expression , 1996, Journal of leukocyte biology.

[14]  J. Giri,et al.  Interaction of IL-15 with the shared IL-2 receptor beta and gamma c subunits. The IL-15/beta/gamma c receptor-ligand complex is less stable than the IL-2/beta/gamma c receptor-ligand complex. , 1996, Journal of immunology.

[15]  I. McInnes,et al.  The role of interleukin–15 in T–cell migration and activation in rheumatoid arthritis , 1996, Nature Medicine.

[16]  N. Copeland,et al.  Functional Characterization of the Human Interleukin-15 Receptor αChain and Close Linkage of IL15RA and IL2RA Genes (*) , 1995, The Journal of Biological Chemistry.

[17]  M. Mohamadzadeh,et al.  Ultraviolet B radiation up-regulates the expression of IL-15 in human skin. , 1995, Journal of immunology.

[18]  M. Wick,et al.  Studies evaluating the antitumor activity and toxicity of interleukin-15, a new T cell growth factor: comparison with interleukin-2. , 1995, Cellular immunology.

[19]  R. Dubose,et al.  Identification and cloning of a novel IL‐15 binding protein that is structurally related to the alpha chain of the IL‐2 receptor. , 1995, The EMBO journal.

[20]  F. Liew,et al.  Interleukin-15 , 2020, Definitions.

[21]  R. Paxton,et al.  IL-15 has stimulatory activity for the induction of B cell proliferation and differentiation. , 1995, Journal of immunology.

[22]  M. Tomonaga,et al.  Established IL‐2‐dependent double‐negative (CD4‐ CD8‐) TCRαβ/CD3+ ATL cells: induction of CD4 expression , 1994 .

[23]  M. Caligiuri,et al.  Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor , 1994, The Journal of experimental medicine.

[24]  D. Cosman,et al.  Utilization of the beta and gamma chains of the IL‐2 receptor by the novel cytokine IL‐15. , 1994, The EMBO journal.

[25]  T. Waldmann,et al.  A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[26]  T. Waldmann,et al.  The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  V. Fung,et al.  Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. , 1994, Science.

[28]  M. Tomonaga,et al.  IL-2-dependent ATL cell lines with phenotypes differing from the original leukemia cells. , 1991, Leukemia research.

[29]  K. Akashi,et al.  Central nervous system involvement in adult T‐cell leukemia/lymphoma , 1990, Cancer.

[30]  Kendall A. Smith,et al.  Interleukin-2: inception, impact, and implications. , 1988, Science.

[31]  S. Hanada,et al.  Adult T‐cell leukemia with leukemia cell infiltration into the gastrointestinal tract , 1988, Cancer.

[32]  M. Siekevitz,et al.  Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[33]  K. Yamaguchi,et al.  Pulmonary complications in patients with adult T‐cell leukemia , 2006 .

[34]  Y. Yamada.  Phenotypic and functional analysis of leukemic cells from 16 patients with adult T-cell leukemia/lymphoma. , 1983, Blood.

[35]  M. Yoshida,et al.  Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[36]  John D. Minna,et al.  Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma , 1980, Proceedings of the National Academy of Sciences.

[37]  J. Yodoi,et al.  Adult T-cell leukemia: clinical and hematologic features of 16 cases. , 1977, Blood.

[38]  H. Towler,et al.  Adult T-cell leukemia : antigen in an ATL cell line and detection of antibodies to the antigen in human sera , 2022 .