P-selectin and P-selectin glycoprotein ligand 1 mediate rolling of activated CD8+ T cells in inflamed colonic venules.

摘要

BACKGROUND: Activated T cells regulate inflammatory diseases in the intestinal tract; however, the adhesive mechanisms governing CD8 T-cell recruitment in the colon are not known. METHODS: Herein, we used a graft-versus-host disease (GvHD) model to study CD8 T-cell rolling and adhesion in the large intestine by use of intravital fluorescence microscopy. Graft-versus-host disease was induced by transferring 50 x 10 allogeneic donor splenocytes from BDF1, B6, H-2b mice to recipient BDF1, H-2 mice. After 8 days, rhodamine-labeled CD8 T cells (4 x 10) from healthy and GvHD mice were injected into both healthy and GvHD recipient mice, and CD8 T-cell-endothelium interactions were studied in the colon. RESULTS: Activated CD8 T cells from GvHD mice expressed higher levels of P-selectin ligand and decreased levels of L-selectin. Immunoneutralization of P-selectin and P-selectin glycoprotein ligand 1 reduced CD8 T-cell rolling and adhesion in inflamed colonic venules by more than 71%. Inhibition of E-selectin had no effect on GvHD-induced CD8 T-cell-endothelium interactions. CONCLUSIONS: We conclude that P-selectin and P-selectin glycoprotein ligand 1 are dominating molecules in supporting adhesive interactions of CD8 T cells in inflamed colonic venules and may be useful targets to protect against pathological inflammation in the large bowel.