Recirculation, phenotype and functions of lymphocytes in mice treated with monoclonal antibody MEL‐14

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Abstract
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.