Platelet MHC-I mediates CD8⁺ T-cell suppression during sepsis in vivo. (A) To study the function of platelet MHC-I function in vivo, we used a platelet lineage–specific B2M knockout strain (B2M^f/f -Pf4Cre). A representative western blot probed for B2M in platelets from a B2M^f/f-Pf4Cre mouse and littermate B2^M+/+ control mouse is shown. (B) B2M^+/+ or B2M^f/f-Pf4Cre mice were subjected to sham or CLP and euthanized on day 4. H-2D expression on platelets was measured by flow cytometry. Only platelets from B2M^+/+ mice had increased H-2D expression during sepsis. Platelets from B2M^f/f -Pf4Cre mice remained negative and unchanged (n = 7-13). (C) Representative flow plots of the CD8⁺ T-cell population from sham or CLP mouse mesenteric lymph nodes. B2M^+/+ mice had decreased CD8⁺ T cells when subjected to CLP, whereas the B2M^f/f-Pf4Cre mice did not. (D-E) Summarized CD8⁺ T-cell frequencies and absolute numbers, CD44^highCD8⁺ T-cell frequencies, and CD4⁺ T-cell frequencies in the mesenteric lymph nodes (D) and peripheral blood (E) (n = 10-24). Upper bracket compares the percentage of CD8⁺ T cells between littermate control sham (eg, baseline) and B2M knockout during CLP. This bracket is included to visually highlight that the absence of MHC-I results in near-normal levels of CD8⁺ T cells during sepsis. One-way analysis of variance with Tukey post hoc analysis was used. *P < .05, **P < .01, ***P < .001. ns, not significant.