Intravital microscopy identifies selectins that regulate T cell traffic into allografts.
T cell homing to sites of injury and inflammation is a critical step for adaptive immune responses. While much has been learned regarding T cell homing to lymphoid tissues, few studies have directly observed trafficking events during an effector response. In this study, we developed a model that uses intravital fluorescence videomicroscopy to determine the molecules critical to T cell rolling within skin allograft microvasculature during the effector phase of the rejection response. Additional studies were performed to quantify T cell infiltrates as rejection progressed. We found that P-selectin and E-selectin expressed on postcapillary venules play overlapping roles in the recruitment of activated T cells in a SCID reconstitution model of skin graft rejection and are important in T cell accumulation at the graft site. Surprisingly, we also found that naive T cells are recruited and accumulate via constitutive T cell L-selectin and upregulated L-selectin ligands on rejecting allograft vasculature. These data indicated that a specific retinue of molecules is upregulated during the rejection response, and they suggest potential future therapeutic targets.
Jones
Thomas R
TR
Emory Transplant Center and Department of Surgery, Emory Universuty School of Medicine, Atlanta, Georgia 30322, USA.
Shirasugi
Nozomu
N
Adams
Andrew B
AB
Pearson
Thomas C
TC
Larsen
Christian P
CP
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D019040:E-Selectin / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology*; D019041:L-Selectin / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018715:Microscopy, Video; D019007:P-Selectin / Q000502:physiology; D019087:Selectins / Q000502:physiology*; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000502:physiology*; D014184:Transplantation, Homologous
D019040:E-Selectin; D019007:P-Selectin; D019087:Selectins; D019041:L-Selectin