L-SELECTIN IS NOT ESSENTIAL FOR NAIVE CD4 CELL TRAFFICKING OR DEVELOPMENT OF PRIMARY RESPONSES IN PEYERS-PATCHES

We showed previously that L-selectin-dependent recirculation of naive CD4 cells is essential for development of primary responses in periphe ral lymph nodes. Recent studies suggest that L-selectin is also requir ed for lymphocyte entry into gut mucosal lymphoid tissues that include Peyer's patches and mesenteric lymph nodes. Here we show that anti-L- selectin antibody, MEL-14, inhibited homing of a rigorously purified, homogenous population of naive CD4 cells into both of these tissues as well as peripheral lymph nodes, directly demonstrating a role for thi s receptor in regulating entry into gut-associated sites. However, in intact animals, treatment with MEL-14 resulted in the loss of naive CD 4 cells (CD45RB(hi), CD44(lo)) from peripheral lymph nodes but not Pey er's patches, whereas mesenteric lymph nodes were intermediate in this regard. In mice grimed by parenteral immunization with keyhole limpet hemocyanin (KLH), primary CD4 responses were readily detected in both Peyer's patches and mesenteric lymph nodes, and were not affected by exposure to MEL-14. Indeed, similar frequencies of KLH-specific CD4 ce lls were recovered from both of these tissues irrespective of MEL-14 t reatment. The results indicate that interactions with L-selectin can b e circumvented to allow entry of naive CD4 cells into Peyer's patches but not peripheral lymph nodes.