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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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Autores principales: Tanaka, Yuetsu, Tanaka, Reiko, Imaizumi, Naoki, Mizuguchi, Mariko, Takahashi, Yoshiaki, Hayashi, Masaki, Miyagi, Takashi, Uchihara, Junnosuke, Ohshiro, Kazuiku, Masuzaki, Hiroaki, Fukushima, Takuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513378/
https://www.ncbi.nlm.nih.gov/pubmed/36177005
http://dx.doi.org/10.3389/fimmu.2022.921606
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author Tanaka, Yuetsu
Tanaka, Reiko
Imaizumi, Naoki
Mizuguchi, Mariko
Takahashi, Yoshiaki
Hayashi, Masaki
Miyagi, Takashi
Uchihara, Junnosuke
Ohshiro, Kazuiku
Masuzaki, Hiroaki
Fukushima, Takuya
author_facet Tanaka, Yuetsu
Tanaka, Reiko
Imaizumi, Naoki
Mizuguchi, Mariko
Takahashi, Yoshiaki
Hayashi, Masaki
Miyagi, Takashi
Uchihara, Junnosuke
Ohshiro, Kazuiku
Masuzaki, Hiroaki
Fukushima, Takuya
author_sort Tanaka, Yuetsu
collection PubMed
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.
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spelling pubmed-95133782022-09-28 A protective role of HTLV-1 gp46-specific neutralizing and antibody-dependent cellular cytotoxicity-inducing antibodies in progression to adult T-cell leukemia (ATL) Tanaka, Yuetsu Tanaka, Reiko Imaizumi, Naoki Mizuguchi, Mariko Takahashi, Yoshiaki Hayashi, Masaki Miyagi, Takashi Uchihara, Junnosuke Ohshiro, Kazuiku Masuzaki, Hiroaki Fukushima, Takuya Front Immunol Immunology 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. Frontiers Media S.A. 2022-09-13 /pmc/articles/PMC9513378/ /pubmed/36177005 http://dx.doi.org/10.3389/fimmu.2022.921606 Text en Copyright © 2022 Tanaka, Tanaka, Imaizumi, Mizuguchi, Takahashi, Hayashi, Miyagi, Uchihara, Ohshiro, Masuzaki and Fukushima https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tanaka, Yuetsu
Tanaka, Reiko
Imaizumi, Naoki
Mizuguchi, Mariko
Takahashi, Yoshiaki
Hayashi, Masaki
Miyagi, Takashi
Uchihara, Junnosuke
Ohshiro, Kazuiku
Masuzaki, Hiroaki
Fukushima, Takuya
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 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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513378/
https://www.ncbi.nlm.nih.gov/pubmed/36177005
http://dx.doi.org/10.3389/fimmu.2022.921606
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