A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL)
Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells....
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.921606/full |
| _version_ | 1798001041931763712 |
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| author | Yuetsu Tanaka Reiko Tanaka Naoki Imaizumi Mariko Mizuguchi Yoshiaki Takahashi Masaki Hayashi Takashi Miyagi Junnosuke Uchihara Kazuiku Ohshiro Hiroaki Masuzaki Takuya Fukushima |
| author_facet | Yuetsu Tanaka Reiko Tanaka Naoki Imaizumi Mariko Mizuguchi Yoshiaki Takahashi Masaki Hayashi Takashi Miyagi Junnosuke Uchihara Kazuiku Ohshiro Hiroaki Masuzaki Takuya Fukushima |
| author_sort | Yuetsu Tanaka |
| collection | DOAJ |
| description | Human T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection. |
| first_indexed | 2024-04-11T11:29:49Z |
| format | Article |
| id | doaj.art-f75639858ad049f7acad21f03e523bcc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T11:29:49Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f75639858ad049f7acad21f03e523bcc2022-12-22T04:26:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.921606921606A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL)Yuetsu Tanaka0Reiko Tanaka1Naoki Imaizumi2Mariko Mizuguchi3Yoshiaki Takahashi4Masaki Hayashi5Takashi Miyagi6Junnosuke Uchihara7Kazuiku Ohshiro8Hiroaki Masuzaki9Takuya Fukushima10Laboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, JapanLaboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, JapanLaboratory of Clinical Physiology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, JapanDepartment of Investigative Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, JapanDepartment of Investigative Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, JapanDepartment of Hematology, Nakagami Hospital, Okinawa, JapanDepartment of Hematology, Heart Life Hospital, Nishihara, JapanDepartment of Hematology, Naha City Hospital, Naha, JapanDepartment of Hematology, Okinawa Prefectural Nambu Medical Center and Children’s Medical Center, Minami-Haebaru, JapanDivision of Endocrinology, Diabetes, and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Nishihara, JapanLaboratory of Hemato-Immunology, Graduate School of Health Sciences, University of the Ryukyus, Nishihara, JapanHuman T-cell leukemia virus type-1 (HTLV-1) establishes a long-term persistent infection in humans and causes malignant T-cell leukemia, adult T-cell leukemia (ATL). HTLV-1-specific cytotoxic T lymphocytes have been suggested to play a major role in the immunosurveillance of HTLV-1-infected T cells. However, it remains unclear whether HTLV-1-specific functional antibodies are also involved in the host defense. To explore the role of antibodies in the course of HTLV-1 infection, we quantitated HTLV-1-specific neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-inducing antibody levels in plasma from asymptomatic carriers (ACs) and ATL patients. The levels of neutralizing antibodies, as determined by a syncytium inhibition assay, were significantly lower in acute and chronic ATL patients than in ACs. The levels of ADCC-inducing activity were tested using an autologous pair of HTLV-1-producing cells and cultured natural killer (NK) cells, which showed that the ADCC-inducing activity of IgG at a concentration of 100 µg/ml was comparable between ACs and acute ATL patients. The anti-gp46 antibody IgG levels, determined by ELISA, correlated with those of the neutralizing and ADCC-inducing antibodies. In contrast, the proviral loads did not correlate with any of these antibody levels. NK cells and a monoclonal anti-gp46 antibody reduced the number of HTLV-1 Tax-expressing cells in cultured peripheral blood mononuclear cells from patients with aggressive ATL. These results suggest a protective role for HTLV-1 neutralizing and ADCC-inducing antibodies during the course of HTLV-1 infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.921606/fullATLHTLV-1antibodyneutralizationADCCgp46 |
| spellingShingle | Yuetsu Tanaka Reiko Tanaka Naoki Imaizumi Mariko Mizuguchi Yoshiaki Takahashi Masaki Hayashi Takashi Miyagi Junnosuke Uchihara Kazuiku Ohshiro Hiroaki Masuzaki Takuya Fukushima A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL) Frontiers in Immunology ATL HTLV-1 antibody neutralization ADCC gp46 |
| title | A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL) |
| title_full | A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL) |
| title_fullStr | A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL) |
| title_full_unstemmed | A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL) |
| title_short | A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL) |
| title_sort | protective role of htlv 1 gp46 specific neutralizing and antibody dependent cellular cytotoxicity inducing antibodies in progression to adult t cell leukemia atl |
| topic | ATL HTLV-1 antibody neutralization ADCC gp46 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.921606/full |
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