{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T01:06:04Z","timestamp":1774400764887,"version":"3.50.1"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["HHSN26120080001E"],"award-info":[{"award-number":["HHSN26120080001E"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              An estimated 10\u201320 million people worldwide are infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). Although most infected individuals remain asymptomatic, some progress to develop the fatal and debilitating disease adult T-cell leukemia\/lymphoma (ATLL) or HTLV-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) or develop a plethora of other inflammatory disorders. In addition, HTLV-1 infection is associated with immunosuppression and a shorter lifespan. Although a protective role for neutralizing antibodies has been suggested, the role of non-neutralizing antibody-dependent cell-mediated cytotoxicity (ADCC) remains unclear, largely because an assay to measure this response has not been established. Here, we developed a high-throughput flow cytometry-based assay system to measure HTLV-1 envelope-specific ADCC. We used a natural killer cell-resistant T-lymphoblastoid cell line stably expressing the green fluorescent protein GFP to construct a target cell line expressing HTLV-1 envelope protein and using monoclonal antibodies and plasma samples from HTLV-infected or uninfected individuals, validating the specificity and sensitivity of the assay. We detected high ADCC activity in samples from HTLV-1-infected humans. In the plasma of experimentally infected macaques, ADCC activity was measured and a correlation between ADCC activity and HTLV-1 envelope antibody titers was observed. Further, we observed a significant increase in ADCC titer over time; as HTLV-1 infection persists, a higher ADCC response is generated, potentially influencing disease outcome. ADCC titer in HTLV-1-infected macaques also positively correlated with FLT3LG, IL-17F, CD4\n              <jats:sup>+<\/jats:sup>\n              T cells, and lymphocytes but negatively correlated with monocyte frequency and classical monocyte frequency. In conclusion, these findings detail the generation of a cell line that enabled development of an HTLV-specific ADCC assay, which can be employed in large clinical studies as well as research involving humans or non-human primates.\n            <\/jats:p>\n            <jats:p\/>\n            <jats:p\/>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>This approach measures human T-cell leukemia virus (HTLV)-specific envelope antibody-dependent cell-mediated cytotoxicity responses, provides a critical tool to investigate the role of envelope-specific binding antibodies in the immune control of HTLV infection and pathogenesis, and may help guide the development of both therapeutic and preventative vaccine approaches.<\/jats:p>\n            <\/jats:sec>\n          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