Platelet MHC-I mediates increased interactions between platelets and antigen-specific CD8⁺ T cells during sepsis. (A) To study whether the antigen–MHC-I complex on platelets can directly engage antigen-specific CD8⁺ T cells, platelets were isolated from either sham or CLP mice, pulsed with SIIN for 2 hours, washed, seeded onto fibrinogen-coated chamber wells, and cocultured with SIIN:H-2K^b-specific CD8⁺ T cells from Rag2^−/− OT-I mice. Unbound cells were washed off. Attached CD8⁺ T cells were fixed and stained for confocal immunofluorescent imaging. (B) Representative Z stack maximum projection images showing an increased number of CD8⁺ T cells (labeled with 4′,6-diamidino-2-phenylindole [DAPI] and CD8) attached to platelets (labeled with GPIb) from CLP mice compared with sham mice. Yellow arrows illustrate CD8⁺ T cells that are attached to platelets. (C) Quantification of CD8⁺ T cells per image shows the interaction between platelets and CD8⁺ T cells in an antigen-specific manner (n = 15). One-way analysis of variance with Tukey post hoc analysis was used. **P < .01, ****P < .0001. ns, not significant.