Cytokines induce lymphocyte migration in vitro by direct, receptor-specific mechanisms

Several cytokines have been found to induce human peripheral blood lymphocyte (PBL) migration in vitro. The mechanisms involved are unclear, therefore experiments were carried out to determine whether PBL migration in response to selected cytokines is due to a direct effect, or to the generation of nonspecific secondary mediators, and whether migration is receptor specific. Purified human PBL were incubated with the lymphocyte chemotactic cytokines interleukin (IL)-1 alpha and IL-8, followed after 30-60 min by addition of specific neutralizing monoclonal antibody. Supernatants of these mixtures were shown by subsequent assay to be devoid of PBL attractant activity, whereas positive control supernatants containing no antibody induced dilution-related migration. Addition of antibody to the high affinity IL-2 receptor abolished the potent attractant effect of IL-2 on PBL, but had little effect on responses to IL-1 alpha and IL-8. These results demonstrate that the in vitro locomotor responses of human PBL to selected cytokines are due to direct, receptor-specific effects and are not dependent upon the generation of secondary mediator(s).