P-selectin and P-selectin glycoprotein ligand 1 mediate rolling of activated CD8+ T cells in inflamed colonic venules.
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.
Asaduzzaman
Muhammad
M
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
Mihaescu
Andrada
A
Wang
Yusheng
Y
Sato
Tohru
T
Thorlacius
Henrik
H
D019264:Adoptive Transfer; D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D003092:Colitis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D019040:E-Selectin / Q000235:genetics / Q000502:physiology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D036904:Leukocyte Rolling / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014699:Venules / Q000276:immunology / Q000473:pathology
D017931:DNA Primers; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D012333:RNA, Messenger