| Naive lymphocytes and central memory T cells continually traffic between the circulation and secondary lymphoid organs, including peripheral lymph nodes (PLN). The initial step of the adhesion cascade by which lymphocytes migrate to PLN is predominantly mediated by the binding of lymphocyte-expressed L-selectin to its ligand, peripheral node addressin (PNAd), in high endothelial venules (HEV). Here we report that HEV-expressed P-selectin contributes to physiological, constitutive lymphocyte homing to PLN. P-selectin plays a significant role in the homing of WT lymphocytes, and a critical one in the homing of L-selectin-deficient lymphocytes, to PLN. WT lymphocytes rolled in PLN HEV of P-selectin-deficient (P-/-) mice less frequently than in those of WT mice. Blocking P-selectin with antibody in WT mice also resulted in higher lymphocyte rolling velocities in PLN HEV. Lymphocyte rolling occurred at regular if low frequency in the PLN HEV of L-selectin-deficient (L-/-) mice, but was virtually absent in P- and L-selectin-doubly-deficient (PL-/-) mice. Experiments with bone marrow chimeric mice revealed that endothelial P-selectin, rather than platelet P-selectin, provided the dominant contribution to this homing mechanism. Moreover, the contribution of endothelial P-selectin expression to constitutive naive lymphocyte homing is immunologically relevant, as PL -/- mice displayed a greater defect in contact hypersensitivity (CHS) responses than did L-/- mice. We conclude that naive T cells express functional P-selectin ligands at low levels, which are recognized by constitutively expressed P-selectin on high endothelial cells in PLN. P-selectin-mediated lymphocyte homing enhances the L-selectin-dependent homing of naive lymphocytes to PLN and may also facilitate the homing of small numbers of P-selectin-ligand+ L-selectin- cells, such as effector T cells, to PLN. To our knowledge, this is the first evidence of constitutive P-selectin expression on PLN HEV, as well as the first documentation of its role in lymphocyte homing. |
