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Cited by 326T-cell and Retrovirus StudiesChemokine receptors and signalingViral-associated cancers and disorders

Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells

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Yoshie, Osamu, Fujisawa, Ryuichi, Nakayama, Takashi, Harasawa, Hitomi, Tago, Hideaki, Izawa, Dai, Hieshima, Kunio, Tatsumi, Youichi +5 more·2002·Blood
DOI 10.1182/blood.v99.5.1505
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Abstract

Chemokines and chemokine receptors play important roles in migration and tissue localization of various lymphocyte subsets. Here, we report the highly frequent expression of CCR4 in adult T-cell leukemia (ATL) and human T-cell leukemia virus type 1 (HTLV-1)–immortalized T cells. Flow cytometric analysis revealed that ATL and HTLV-1–immortalized T-cell lines consistently expressed CCR4. Inducible expression of HTLV-1 transcriptional activator tax in a human T-cell line Jurkat did not, however, up-regulate CCR4 mRNA. In vitro immortalization of peripheral blood T cells led to preferential outgrowth of CD4+ T cells expressing CCR4. We further demonstrated highly frequent expression of CCR4 in fresh ATL cells by (1) reverse transcriptase–polymerase chain reaction (RT-PCR) analysis of CCR4 expression in peripheral blood mononuclear cells (PBMCs) from patients with ATL and healthy controls; (2) flow cytometric analysis of CCR4-expressing cells in PBMCs from patients with ATL and healthy controls; (3) CCR4 staining of routine blood smears from patients with ATL; and (4) an efficient migration of fresh ATL cells to the CCR4 ligands, TARC/CCL17 and MDC/CCL22, in chemotaxis assays. Furthermore, we detected strong signals for CCR4, TARC, and MDC in ATL skin lesions by RT-PCR. Collectively, most ATL cases have apparently derived from CD4+ T cells expressing CCR4. It is now known that circulating CCR4+ T cells are mostly polarized to Th2 and also contain essentially all skin-seeking memory T cells. Thus, HTLV-1–infected CCR4+ T cells may have growth advantages by deviating host immune responses to Th2. CCR4 expression may also account for frequent infiltration of ATL into tissues such as skin and lymph nodes.

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  • Mogamulizumab targets CCR4, a chemokine receptor highly expressed by HTLV-1-infected T cells, with phase I and II clinical trials resulting in an overall response rate (ORR) of 50%.

    “Mogamulizumab targets CCR4, a chemokine receptor highly expressed by HTLV-1-infected T cells [198,199,200], with phase I and II clinical trials resulting in an overall response rate (ORR) of 50% [201,202,203].”

    From Current State of Therapeutics for HTLV-1 (2024) · cites this paper as [198]

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Research works printed but not linked: 3

  1. [28]28. Loetscher M, Gerber B, Loetscher P, et al. Che- mokine receptor specific for IP10 and mig: struc- ture, function, and expression in activated T-lym- phocytes. J Exp Med. 1996;184:963-969.
  2. [39]39. Baba M, Imai T, Yoshida T, Yoshie O. Constitutive expression of various chemokine genes in human T-cell lines infected with human T-cell leukemia virus type 1: role of the viral transactivator Tax. Int J Cancer. 1996;66:124-129.
  3. [47]47. Kanazawa N, Nakamura T, Tashiro K, et al. Frac- talkine and macrophage-derived chemokine: T cell-attracting chemokines expressed in T cell area dendritic cells. Eur J Immunol. 1999;29: 1925-1932.

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Authors
Yoshie, O., Fujisawa, R., Nakayama, T., Harasawa, H., Tago, H., Izawa, D., Hieshima, K., Tatsumi, Y., Matsushima, K., Hasegawa, H., Kanamaru, A., Kamihira, S., & Yamada, Y.
Affiliations
Tohoku University (JP)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2002-03-01
Volume
99
Issue
5
Pages
1505-1511
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v99.5.1505
OpenAlex
W2110220145
Cited by
326
References
49
Citations by year
2026: 6 · 2025: 9 · 2024: 11 · 2023: 15 · 2022: 11 · 2021: 22 · 2020: 15 · 2019: 19 · 2018: 17 · 2017: 18 · 2016: 13 · 2015: 16 · 2014: 23 · 2013: 14 · 2012: 9
FWCI
2.73
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Keywords
CCR4, adult T-cell leukemia/lymphoma, HTLV-1, chemokine receptors, TARC/CCL17, MDC/CCL22, chemotaxis, CD4+ T cells, Th2 polarization, skin lesions, lymph node invasion, T-cell immortalization
MeSH terms
Adult, Aged, Aged, 80 and over, Cell Line, Transformed, Chemotaxis, Leukocyte, Female, Humans, Male, Middle Aged, RNA, Messenger, Skin, T-Lymphocytes, Human T-lymphotropic virus 1, Leukemia-Lymphoma, Adult T-Cell, Gene Products, tax, Jurkat Cells, Receptors, Chemokine, Chemokines, CC, Receptors, CCR4

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