CD8⁺ T cells interact with platelets causing T-cell activation, IFN-γ release, and CD107a and platelet activation. CD8⁺ T-cell–platelet aggregates are inhibited with MHC class I blocking on platelets. (A) When CD8⁺ T cells flow along a chamber coated with platelets, CD8⁺ T cells from patients with ITP were 4 times more likely to slow down and stop along the platelet coated surface than controls. (B) Confocal imaging of CD8⁺ T-cell interactions with platelets in a patient with ITP (×20 lens objective). (C) Example of a dot plot from flow cytometry analysis of a control vs patient with ITP when CD8⁺ T cells are cocultured with platelets, showing CD8⁺ T-cell–platelet aggregates (CD8⁺CD41⁺) from total CD8⁺ T cells. (D) CD8⁺ T-cell–platelet aggregates are higher in patients with ITP than in healthy controls and (E) are inhibited when MHC class I HLA-A, -B, and -C receptors on platelets are blocked. (F) In CD8⁺ T-cell–platelet coculture, (G) CD107a is increased in the CD8⁺ T-cell–platelet aggregates compared with CD8⁺ T cells cultured alone, consistent with release of granzyme B; (H) platelets in the CD8⁺ T-cell–platelet aggregates show increased CD62P, consistent with platelet activation. (I) IFN-γ ELISpot assay of T cells cultured with autologous platelets shows that T cells from patients with ITP have increased secretion of IFN-γ when cultured with platelets (detected by IFN-γ–forming spots). ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001. HC, healthy control; SEB, staphylococcal enterotoxin.