Human V9V2 T cells exhibit antifungal activity against Aspergillus fumigatus and other filamentous fungi

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant Aspergillus fumigatus 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 gamma 9V delta 2 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 A. fumigatus (Af293) hyphae were challenged by V gamma 9V delta 2 T cells derived from peripheral blood. In addition, V gamma 9V delta 2 T cells exhibited antifungal activity against hyphae of all Aspergillus spp., Cunninghamella bertholletiae, and Rhizopus microsporus but not against their conidia. Furthermore, V gamma 9V delta 2 T cells also exhibited antifungal activity against azole-resistant A. fumigatus, indicating that V gamma 9V delta 2 T cells could be used for treating drug-resistant A. fumigatus. The antifungal activity of V gamma 9V delta 2 T cells depended on cell-to-cell contact with A. fumigatus hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against A. fumigatus. V gamma 9V delta 2 T cells could be developed as a novel modality for treating IA or mucormycosis.