MODULATION OF IL-8 RECEPTOR EXPRESSION ON PURIFIED HUMAN T-LYMPHOCYTES IS ASSOCIATED WITH CHANGED CHEMOTACTIC RESPONSES TO IL-8

Interleukin-8 is a member of the chemokine superfamily and is a major mediator of acute inflammation. Although IL-8 has been reported by som e laboratories also to be a chemoattractant for T lymphocytes, this ha s been difficult to confirm and remains a controversial issue. By usin g freshly purified human T cells (90-95 % CD3(+)), we could demonstrat e consistent directional migration of T cells to recombinant human IL- 8. IL-8 was as potent as RANTES, MIP1 alpha, and MIP1 beta in inducing T cell chemotaxis. Highly purified T cells, however, incubated at 37 degrees C for more than 12 h or cultured overnight with anti-CD3 antib ody cross-linked to plastic dishes, showed a markedly reduced capacity to migrate in response to IL-8. This was associated with a decrease i n binding of radioiodinated IL-8 to T cells. Northern blot and polymer ase chain reaction analyses showed that freshly purified T cells expre ssed mRNA for both IL-8 receptor type A and type B. Steady-state level s of mRNA for the IL-8RA and IL-8RB genes were also reduced by incubat ion of the cells with or without anti-CD3 for 12 h at 37 degrees C. Th ese results indicate that T cells are indeed one of the target cell po pulations for IL-8. The regulation of IL-8 receptor expression on T ly mphocytes may contribute to the pathophysiological role of IL-8 in ind ucing the homing and infiltration of T cells.