L-SELECTIN IS INVOLVED IN LYMPHOCYTE MIGRATION TO SITES OF INFLAMMATION IN THE SKIN - DELAYED REJECTION OF ALLOGRAFTS IN L-SELECTIN-DEFICIENT MICE

Adhesion of leukocytes to vascular endothelium is crucial for leukocyt e migration into tissues. The contributions of L-selectin, P-selectin, and ICAM-1 to interactions between lymphocytes and endothelium was ex amined using allogeneic skin graft rejection as a model of cutaneous i nflammation, L-selectin-deficient (L-selectin(-/-)) mice rejected both primary and secondary allogeneic (BALB/c) skin grafts significantly m ore slowly than L-selectin(+/+) littermates. Furthermore, skin graft r ejection remained significantly delayed in L-selectin(-/-) mice, despi te placement of grafts 7 days after i.p. immunization with allogeneic cells, when CTL responses in L-selectin(-/-) mice and L-selectin(+/+) littermates were confirmed to be equivalent. Indeed, specific CTL resp onses to BALB/c splenocytes were normal or elevated in L-selectin(-/-) mice following either skin grafts or immunization, However, the numbe r of T lymphocytes within allogeneic grafts was lower in L-selectin(-/ -) mice as compared with L-selectin(+/+) littermates. Therefore, delay ed rejection of skin grafts by L-selectin(-/-) mice reflects impaired migration of effector cells into the graft rather than delayed or impa ired generation of a CTL response. In contrast to L-selectin(-/-) mice , P-selectin-deficient and ICAM-1-deficient mice rejected allogeneic s kin grafts normally. These findings delineate an important role for L- selectin in lymphocyte recruitment to cutaneous sites of inflammation.