P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules

Abstract

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 × 10⁶ allogeneic donor splenocytes from BDF1, B6, H-2b mice to recipient BDF1, H-2^bxd mice. After 8 days, rhodamine-labeled CD8⁺ T cells (4 × 10⁶) 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.