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 I L-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 a nd 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 prolife ration was higher for the CD4+ than for the CD 8+ 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-res ponsive CD8+ crones seemed to represent a minor subset expressing the pheno type CD4(low)CD8(high). The anti-CD3-stimulated polyclonal responses were g enerally lower for the cytopenic patients than for healthy individuals, and this decreased responsiveness was probably caused by a combination of quan titative T cell defects and suboptimal accessory cell costimulation. Althou gh IL-16 and IL-17 could function as growth factors for a large subset of o ur 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 enhance ment of anti-CD3 and anti-CD3+anti-CD28 responses, no alteration of the cyt okine responsiveness profile after anti-CD3 stimulation). We conclude that both IL-16 and IL-17 are potentially immunostimulatory cytokines in patient s with acute leukemia and chemotherapy-induced leukopenia, but the final ef fects of IL-16/IL-17 on proliferative T cell responses are modulated by loc al immunoregulatory networks. Copyright (C) 2001 S. Karger AG, Basel.