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The Dependency of Double-Negative T Cell-Mediated Antitumor Immunity on IFN-g, Perforin, and MHC molecules 2201

Year: 2025
Type: article
Abstract: Description A large body of published data has unequivocally indicated that TCRab+CD4-CD8- double-negative T (DN T) cells play a critical role in autoimmune diseases, infectious diseases, and cancer in humans and mice. Using a specific T cell receptor Ja281knockout (KO) mouse model, we found that DN T cells play a crucial role in initiating antitumor immune response and shaping tumor microenvironment. However, the precise mechanism remains elucidated. Herein, we used specific gene KO mice, adoptive cell transfer, and E0771, B16BL6, and 3LL tumor models to study the dependency of DN T cell-mediated antitumor immunity on IFN-g, perforin, and MHC molecules. When transferring IFN-g KO or perforin KO DN T cells into Ja281 KO mice, the cell transfer-induced antitumor immunity in Ja281 KO mice was maintained, suggesting that DN T cell-mediated antitumor immunity is independent of DN T cell-produced IFN-g or perforin. Transferring B2m KO, MHC II KO, or B2m/MHC II double KO DN T cells into Ja281 KO mice did not affect DN T transfer-induced antitumor immunity. Transferring wild-type (WT) DN T cells into the MHC II KO mice did not induce antitumor immunity. However, transferring WT DN T cells into the MHC I KO mice induced the same effective antitumor immunity as DN T cell transfer-induced antitumor immunity in Ja281 KO mice. These results indicate that DN T cell-mediated antitumor immunity is independent of MHC II and ND T-produced IFN-g and perforin but in an MHC I-dependent/independent manner. Funding Sources This work was supported by the NIH/NCI grant R01CA276284 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)
DOI: 10.1093/jimmun/vkaf283.148
Authors: Hui Zhang, Anil Singh
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416447238
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