Academic Journal
IL-2/IL-2 Receptor Pathway Plays a Crucial Role in the Growth and Malignant Transformation of HTLV-1-Infected T Cells to Develop Adult T-Cell Leukemia
| Title: | IL-2/IL-2 Receptor Pathway Plays a Crucial Role in the Growth and Malignant Transformation of HTLV-1-Infected T Cells to Develop Adult T-Cell Leukemia |
|---|---|
| Authors: | Michiyuki Maeda, Junko Tanabe-Shibuya, Paola Miyazato, Hiroshi Masutani, Jun-ichirou Yasunaga, Kazumasa Usami, Akira Shimizu, Masao Matsuoka |
| Superior Title: | Frontiers in Microbiology, Vol 11 (2020) |
| Publisher Information: | Frontiers Media S.A. |
| Publication Year: | 2020 |
| Collection: | Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: | adult T-cell leukemia, human T-cell leukemia virus type 1, IL-2/IL-15/IL-2R, Tax, HBZ, p53, Microbiology, QR1-502 |
| Description: | T cells infected with human T-cell leukemia virus type 1 (HTLV-1) transform into malignant/leukemic cells and develop adult T-cell leukemia (ATL) after a long latency period. The tax (transactivator from the X-gene region) and HBZ (HTLV-1 bZIP factor) genes of HTLV-1 play crucial roles in the development of ATL. The process and mechanism by which HTLV-1-infected T cells acquire malignancy and develop ATL remain to be elucidated. Constitutive expression of interleukin-2 (IL-2) receptor α-chain (IL-2Rα/CD25), induced by the tax and HBZ genes of HTLV-1, on ATL cells implicates the involvement of IL-2/IL-2R pathway in the growth and development of ATL cells in vivo. However, the leukemic cells in the majority of ATL patients appeared unresponsive to IL-2, raising controversies on the role of this pathway for the growth of ATL cells in vivo. Here, we report the establishment of 32 IL-2-dependent T-cell lines infected with HTLV-1 from 26 ATL patients, including eight leukemic cell lines derived from five ATL patients, while no T-cell lines were established without IL-2. We have shown that the IL-2-dependent ATL cell lines evolved into IL-2-independent/-unresponsive growth phase, resembling ATL cells in vivo. Moreover, the IL-2-dependent non-leukemic T-cell lines infected with HTLV-1 acquired IL-2-independency and turned into tumor-producing cancer cells as with the ATL cell lines. HTLV-1-infected T cells in vivo could survive and proliferate depending on IL-2 that was produced in vivo by the HTLV-1-infected T cells of ATL patients and patients with HTLV-1-associated diseases and, acts as a physiological molecule to regulate T-cell growth. These results suggest that ATL cells develop among the HTLV-1-infected T cells growing dependently on IL-2 and that most of the circulating ATL cells progressed to become less responsive to IL-2, acquiring the ability to proliferate without IL-2. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| ISSN: | 1664-302X |
| Relation: | https://www.frontiersin.org/article/10.3389/fmicb.2020.00356/full; https://doaj.org/toc/1664-302X; https://doaj.org/article/018f49d0cb2d45cf8716494c8482b56d |
| DOI: | 10.3389/fmicb.2020.00356 |
| Availability: | https://doi.org/10.3389/fmicb.2020.00356 https://doaj.org/article/018f49d0cb2d45cf8716494c8482b56d |
| Accession Number: | edsbas.1497357B |
| Database: | BASE |
| Description not available. |