Author:
Takahiro Takazono (JP)
Abstract:
Objective
Invasive pulmonary aspergillosis (IPA) or mucoromycosis is a life-threatening disease affecting immunocompromised patients. Recently, drug-resistant strains of A. fumigatus have been isolated worldwide, which would be a serious problem in clinical settings and hospitals in the future because it is difficult to develop a new class of antifungal agents due to the similarity between fungal and human cells, both of which belong to eukaryotic cells. Immunotherapy has received much attention in the last decade following the success of immune checkpoint inhibitors and cell therapy in cancer therapy. Since IA occurs in patients with compromised immune systems, it is reasonable to use a therapeutic approach that enhances the immune system in the treatment of IA. In this study, we focused on Vγ9Vδ2 T cells, which exhibit immune effector functions, and explored the possibility of using the unconventional T cell subset as a novel therapeutic modality for IA.
Methods
Human Vγ9Vδ2 T cells were obtained from a healthy volunteer and expanded by stimulation with PTA and IL-2. The fungicidal activity of Vγ9Vδ2 T cells was evaluated on conidia and hyphae of Aspergillus and several Mucor species using the XTT assay or the CFU assay. In addition, fungicidal activity against cell wall component deficient strains of A. fumigatus was evaluated to estimate the target site of Vγ9Vδ2 T cells. The mechanism of action was also investigated using supernatant cytokines and cell surface antigen expression.
Results
Vγ9Vδ2 T cells showed a fungicidal effect on hyphae but not on conidia of A. fumigatus (Af293). Vγ9Vδ2 T cells also showed fungicidal activity against all other Aspergillus species and some Mucor species. Since it was effective against A. fumigatus⊿uge5 (galactomannan deficient) but not against ⊿uge3 (galactosaminogalactan), the target site is considered to be galactosaminogalactan in A. fumigatus. IFN-γ levels were not increased in the co-culture supernatant. The effect was attenuated by inserting a cell culture insert to prevent direct contact of the two cells. The expression of CD107a was also increased by co-culture, whereas the antifungal activity of the cells was reduced by pretreatment with EGTA. In conclusion, the antifungal activity of Vγ9Vδ2 T cells is induced by direct contact, with cytolytic degranulation as a possible mechanism of action.
Conclusion
Immunotherapy with Vγ9Vδ2 T cells is a potential candidate for a new treatment modality for IPA or mucormycosis in the future. Further evaluation in an in vivo model is needed.
Abstract Number: 44
Conference Year: 2024
Conference abstracts, posters & presentations
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Title
Author
Year
Number
Poster
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v
Ferro, R 1,2; Caeiro, E 1,2; Camacho, I 3; Paiva, M 4; Morais-Almeida, M 5; Nunes, C 6; Brandao, R 2,7
739-B
n/a
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v
Wang, J-Y 1; Chen, C-A 1; Hou, Y-I 1; Hsiao, W-L 1; Huang,Y-W 2; Tsai, Y-T 2; Tsai, H-J 2
1544
n/a
-
v
Park, AL 1; Yoon, J 2; Lee, E 2; Yu, J 2
322
n/a
-
v
Barocci, F1; De Bernardi, G2; Lodato, A1
282
n/a
-
v
Kim, SR1; Lee, YC1; Park, HJ1; Kim, DI1; Kim, SH2
195
n/a
-
v
van Kampen, V1; Hoffmeyer, F1; Deckert, A1; Neumann, H-D2; Buxtrup, M2; Willer, E3; Felten, C3; Bruening, T1; Sander, I1; Raulf, M1; Buenger, J1
190
n/a
-
v
Olaitan Owoyemi 1, 2, Edward Oyekanmi 2
421
n/a
-
v
B. J. Akinyele 1, C. O. Ogidi 2, P. O. Gabriel 1 and O. O. Olaniyi 1
320
n/a
-
v
R. Huseynov and S. Javadov
401
n/a
-
v
Adewale Kayode Ogunyemi 1*, Bukola Caroline Ogunyemi 2, Abiola Lateefat Ategun 2, Bamidele Abiodun Iwalokun 3, Joseph Ikosi Ike 2, Matthew Olusoji Ilori 1 and Olukayode Oladipo Amund 1
353
n/a