biostudies-literatureReithofer MAustrian Science Fund FWF721-733https://www.ebi.ac.uk/biostudies/studies/S-EPMC7986150biostudies-literatureUnknown51(3)Costimulatory signals potently promote T-cell proliferation and effector function. Agonistic antibodies targeting costimulatory receptors of the TNFR family, such as 4-1BB and CD27, have entered clinical trials in cancer patients. Currently there is limited information how costimulatory signals regulate antigen-specific but also bystander activation of human CD8 T cells. Engineered antigen presenting cells (eAPC) efficiently presenting several common viral epitopes on HLA-A2 in combination with MHC class I tetramer staining were used to investigate the impact of costimulatory signals on human CD8 T-cell responses. CD28 costimulation potently augmented the percentage and number of antigen-reactive CD8 T cells, whereas eAPC expressing 4-1BB-ligand induced bystander proliferation of CD8 T celEuropean journal of immunology4-1BB costimulation promotes bystander activation of human CD8 T cells.PMC7986150MCCA‐W1248SFB‐F4610FWF‐P32411Jahn-Schmid BLeitner JRosskopf SBattin CBohle BReithofer MSteinberger Pfalse4-1BB costimulation promotes bystander activation of human CD8 T cells.Costimulatory signals potently promote T-cell proliferation and effector function. Agonistic antibodies targeting costimulatory receptors of the TNFR family, such as 4-1BB and CD27, have entered clinical trials in cancer patients. Currently there is limited information how costimulatory signals regulate antigen-specific but also bystander activation of human CD8 T cells. Engineered antigen presenting cells (eAPC) efficiently presenting several common viral epitopes on HLA-A2 in combination with MHC class I tetramer staining were used to investigate the impact of costimulatory signals on human CD8 T-cell responses. CD28 costimulation potently augmented the percentage and number of antigen-reactive CD8 T cells, whereas eAPC expressing 4-1BB-ligand induced bystander proliferation of CD8 T cel2021-01-01T00:00:00Z2021 Mar2025-04-05T15:24:32.196Z2025-04-05T15:24:32.196ZS-EPMC79861503318033710.1002/eji.202048762