The cellular immune system of patients with acute leukemia and severe chemotherapy-induced leukopenia: characterization of T lymphocyte subsets responsive to IL-16 and IL-17.

The aim of the present study was to characterize the effects of IL-16 and IL-17 on CD4+ and CD8+ T cell responses in patients with acute leukemia and severe chemotherapy-induced leukopenia. We investigated (1) the function of cytokines as growth factors for preactivated monoclonal T cell populations which had been prepared by long-term in vitro culture, and (2) the ability of cytokines to modulate anti-CD3-stimulated proliferation of polyclonal, nonexpanded T cells. A subset of CD4+ and CD8+ clones could utilize IL-16 and IL-17 as growth factors after previous mitogenic activation, but for the CD4+ subset IL-16 responses were significantly higher than IL-17 responses. Cytokine-dependent proliferation was higher for the CD4+ than for the CD8+ clones in the presence of both IL-16 and IL-17. The effects of IL-16/IL-17 were modulated by the presence of exogenous IL-2 and IL-4. The IL-16-responsive CD8+ clones seemed to represent a minor subset expressing the phenotype CD4lowCD8high. The anti-CD3-stimulated polyclonal responses were generally lower for the cytopenic patients than for healthy individuals, and this decreased responsiveness was probably caused by a combination of quantitative T cell defects and suboptimal accessory cell costimulation. Although IL-16 and IL-17 could function as growth factors for a large subset of our T cell clones, both cytokines had either no or only minor effects on the polyclonal T cell responses for cytopenic patients (e.g. only weak enhancement of anti-CD3 and anti-CD3+anti-CD28 responses, no alteration of the cytokine responsiveness profile after anti-CD3 stimulation). We conclude that both IL-16 and IL-17 are potentially immunostimulatory cytokines in patients with acute leukemia and chemotherapy-induced leukopenia, but the final effects of IL-16/IL-17 on proliferative T cell responses are modulated by local immunoregulatory networks.