The neutrophil chemotactic cytokine, IL-8, has been reported to also chemoattract T lymphocytes in vitro and in vivo. Previously we showed that freshly isolated T cells migrated in response to IL-8, but incubation of T cells at 37 degrees C resulted in progressively decreased levels of IL-8 binding sites on T cells in association with reduced chemotactic responses. However, this reduced binding and migration of cultured T cells in response to IL-8 can be prevented by the presence of mononuclear cells in the culture. In order to define the factor(s) responsible for the restoration of T cell binding and migration in response to IL-8, we examined the effects of various cytokines. Addition of IFN-gamma in cultured T cells maintained both the CXC chemokine receptor CXCR1 and CXCR2 binding sites for IL-8 on these cells to the level comparable to that expressed on freshly purified T cells accompanied by an almost complete restoration of their chemotactic response to IL-8. The results suggest that Th1 cytokine, IFN-gamma, produced by mononuclear cells stimulated by proinflammatory signals may play an important role in regulating IL-8 receptor expression on T cells and in sustaining the function of these cells in response to IL-8.