Cytokine responsiveness of mitogen-activated T cells derived from acute leukemia patients with chemotherapy-induced leukopenia

The aim of the study was to characterize effects of exogenous cytokines on T lymphocytes derived from acute leukemia patients with chemotherapy-induce d leukopenia. We investigated the cytokine responsiveness of long-term expa nded CD4(+) and CD8(+) T cell clones and the effects of exogenous cytokines on anti-CD3-stimulated polyclonal T cell responses. After mitogenic activa tion in the presence of acute myelogenous leukemia (AML) blasts, most CD4() and CD8(+) clones proliferated in response to interleukin-2 (IL-2). Altho ugh a majority of the IL-2-responsive clones could also proliferate in the presence of exogenous IL-4, IL-7, IL-9, IL-10, IL-12, and IL-15, only IL-15 responses were equal to or exceeded the corresponding IL-2 responses. Exog enous cytokines were also added during T cell activation with phytohemagglu tinin (PHA) + accessory leukemia cells derived from different AML patients, and all the cytokines then had divergent effects that depended on both dif ferences between clones and differences between AML patients. However, for most of these T cell clone/AML blast combinations, IL-2 and IL-15 caused en hanced T cell proliferation. IL-2 and IL-15 also enhanced anti-CD3-stimulat ed polyclonal responses of nonexpanded T cells derived from cytopenic patie nts, whereas other cytokines had only minor effects. Our results demonstrat e that cytokine-responsive T cells remain in the circulation during chemoth erapy-induced cytopenia, and combination therapy including intensive chemot herapy and T cell-targeting cytokine therapy should, therefore, be possible in AML.