Traffic of L-selectin-negative T cells to sites of inflammation.
T cells responding to antigen in vivo down-regulate L-selectin, the lymph node homing receptor, as they develop into activated effector cells. The concomitant up-regulation of the proinflammatory adhesion molecules LFA-1, CD44, and VLA-4 suggests that, after their release into the circulation, they traffic to sites of antigen deposition and inflammation. Previous evidence, however, has suggested a role for L-selectin in the recruitment of both neutrophils and lymphocytes into sites of inflammation, which would indicate that these L-selectin(-) effector cells could not be the precursors of inflammatory cells. We therefore directly tested whether L-selectin(-) T cells activated in vivo are capable of homing to model inflammatory sites. L-selectin(-) cells isolated from mice primed with alloantigen or with a contact sensitizer migrated to inflammation markedly better than L-selectin(+) cells from the same animals. Furthermore, the analogous population of CD44(hi)integrin(hi) cells from intravenously primed L-selectin knockout mice traffic efficiently to inflammatory sites and reject allogeneic skin grafts with normal kinetics. These data demonstrate that the previously described L-selectin(-) population of T cells that differentiate into effectors in spleen and lymph nodes subsequently traffic to inflammatory sites, due in part to their increased expression of other proinflammatory adhesion molecules.
Rigby
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Department of Microbiology, The University of Iowa College of Medicine, Iowa City, USA.
Dailey
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D000818:Animals; D002465:Cell Movement; D006084:Graft Rejection; D018960:Hyaluronan Receptors / Q000502:physiology; D007249:Inflammation / Q000276:immunology*; D019041:L-Selectin / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000502:physiology*; D014184:Transplantation, Homologous
D018960:Hyaluronan Receptors; D019041:L-Selectin