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Drug-resistant\n              <jats:italic>Aspergillus fumigatus<\/jats:italic>\n              strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on V\u03b39V\u03b42 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when\n              <jats:italic>A. fumigatus<\/jats:italic>\n              (\n              <jats:italic>Af293<\/jats:italic>\n              ) hyphae were challenged by V\u03b39V\u03b42 T cells derived from peripheral blood. In addition, V\u03b39V\u03b42 T cells exhibited antifungal activity against hyphae of all\n              <jats:italic>Aspergillus<\/jats:italic>\n              spp.,\n              <jats:italic>Cunninghamella bertholletiae<\/jats:italic>\n              , and\n              <jats:italic>Rhizopus microsporus<\/jats:italic>\n              but not against their conidia. Furthermore, V\u03b39V\u03b42 T cells also exhibited antifungal activity against azole-resistant\n              <jats:italic>A. fumigatus<\/jats:italic>\n              , indicating that V\u03b39V\u03b42 T cells could be used for treating drug-resistant\n              <jats:italic>A. fumigatus<\/jats:italic>\n              . The antifungal activity of V\u03b39V\u03b42 T cells depended on cell-to-cell contact with\n              <jats:italic>A. fumigatus<\/jats:italic>\n              hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against\n              <jats:italic>A. fumigatus<\/jats:italic>\n              . V\u03b39V\u03b42 T cells could be developed as a novel modality for treating IA or mucormycosis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of V\u03b39V\u03b42 T cells against various\n              <jats:italic>Aspergillus<\/jats:italic>\n              spp. and several\n              <jats:italic>Mucorales in vitro<\/jats:italic>\n              and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using V\u03b39V\u03b42 T cells may offer a new therapeutic approach to IA.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.03614-23","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T14:01:12Z","timestamp":1709301672000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Human V\u03b39V\u03b42 T cells exhibit antifungal activity against\n            <i>Aspergillus fumigatus<\/i>\n            and other filamentous fungi"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9415-2305","authenticated-orcid":false,"given":"Satoru","family":"Koga","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan"},{"name":"Department of Respiratory Medicine, Nagasaki University Hospital, 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