RECIRCULATION PHENOTYPE AND FUNCTIONS OF LYMPHOCYTES IN MICE TREATED WITH MONOCLONAL-ANTIBODY MEL-14

The effect of a single injection of an antibody against the peripheral lymph node (PLN) homing receptor or L-selectin (gp90(MEL-14)) was stu died in vivo in C57BL/6 mice. L-selectin is known to be rapidly shed f rom leukocytes in humans and in mice following activation or cross-lin king in vitro. Here we demonstrate that in vivo a single injection of MEL-14 antibody induces a rapid, almost complete and reversible down-r egulation of L-selectin expression on both T and B cells. This modulat ion is dose dependent, specific for L-selectin and lasts for 10 days. On neutrophils, L-selectin expression was moderately decreased, and th e injected antibody was detectable on the cell surface for several day s. Thus, L-selectin expression after antibody binding in vivo was affe cted differently on neutrophils and lymphocytes. MEL-14 treatment indu ces profound alterations of cell traffic. Loss of L-selectin on lympho cytes leads to drastic PLN depletion and increased spleen cellularity. Depleted PLN were highly enriched in MEL-14(-/lo), CD44(hi) and CD11a (hi) cells, which may represent transiently sessile memory/activated c ells. The unresponsiveness in mixed lymphocyte reaction of PLN cells f rom treated animals and of purified L-selectin(-) PLN T cells from nor mal mice supports this view. However, PLN and spleen cells from treate d animals responded normally to non-antigen-specific stimuli.