RT Journal Article
SR Electronic
T1 P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules
JF Journal of Investigative Medicine
JO J Investig Med
FD BMJ Publishing Group Ltd
SP 765
OP 768
DO 10.2310/JIM.0b013e3181b918fb
VO 57
IS 7
A1 Muhammad Asaduzzaman
A1 Andrada Mihaescu
A1 Yusheng Wang
A1 Tohru Sato
A1 Henrik Thorlacius
YR 2009
UL http://hw-f5-jim.highwire.org/content/57/7/765.abstract
AB 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-2bxd 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.