ENTRY OF NAIVE CD4 T-CELLS INTO PERIPHERAL LYMPH-NODES REQUIRES L-SELECTIN

Binding of L-selectin expressed on lymphocytes to carbohydrate ligand( s) on lymph node high endothelial venules is thought to initiate lymph ocyte extravasation from blood to lymph during recirculation and local ization to sites of antigen (Ag) exposure. Previous studies have shown that treatment of lymphocytes with antibody to L-selectin (MEL-14) ab lates trafficking to peripheral lymph nodes (PLN). In mice, naive but not memory CD4 cells express L-selectin. To examine the role of L-sele ctin in helper T cell migration, we studied the effects of in vivo adm inistration of MEL-14 on CD4 cell responses. Systemic exposure of mice to MEL-14 depleted CD4 cells expressing a naive phenotype (CD45RB(hi) , CD44(lo)) from PLN but not from spleen. The majority of residual lym ph node CD4 cells exhibited the reciprocal, memory phenotype (CD45RB(b ), CD44(hi)). MEL-14 treatment prevented priming of naive CD4 cells fo r proliferation and cytokine production (IL-2 and IL-4) to keyhole lim pet hemocyanin in PLN draining the site of Ag injection, but not in th e spleen. The results suggest that naive cells were not depleted, but rather diverted to other sites where priming occurred. The data demons trate that L-selectin mediates extravasation of naive CD4 cells into P LN and that its function cannot be replaced by other homing receptors.