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 (gp90MEL-14) was studied in vivo in C57BL/6 mice. L-selectin is known to be rapidly shed from leukocytes in humans and in mice following activation or cross-linking in vitro. Here we demonstrate that in vivo a single injection of MEL-14 antibody induces a rapid, almost complete and reversible down-regulation of L-selectin expression on both T and B cells. This modulation is dose dependent, specific for L-selectin and lasts for 10 days. On neutrophils, L-selectin expression was moderately decreased, and the injected antibody was detectable on the cell surface for several days. Thus, L-selectin expression after antibody binding in vivo was affected differently on neutrophils and lymphocytes. MEL-14 treatment induces profound alterations of cell traffic. Loss of L-selectin on lymphocytes leads to drastic PLN depletion and increased spleen cellularity. Depleted PLN were highly enriched in MEL-14-/lo, CD44hi and CD11ahi cells, which may represent transiently sessile memory/activated cells. The unresponsiveness in mixed lymphocyte reaction of PLN cells from treated animals and of purified L-selectin- PLN T cells from normal mice supports this view. However, PLN and spleen cells from treated animals responded normally to non-antigen-specific stimuli.