Normal intrinsic Th1/Th2 balance in patients with chronic phase chronic myeloid leukemia not treated with interferon-alpha or imatinib

Abstract

BACKGROUND AND OBJECTIVES: CD4+ T helper cells are an integral part of effective immune responses against various malignancies; however in tumor-bearing patients they are frequently functionally unresponsive. T helper cells of patients with chronic myeloid leukemia (CML), analyzed as part of mononuclear cell fractions, show a loss of signaling molecules, a compromised Th1 cytokine production and a shift towards a non-productive Th2 state. The underlying mechanism is unknown and may involve intrinsic T cell defects as well as indirect effects mediated by leukemia or antigen-presenting cells. The purpose of the present study was to analyze the intrinsic cytokine-producing capacity of purified CML T helper cells in the absence of other cell types. DESIGN AND METHODS: Untouched CD4+ T cells with a purity of more than 90% were isolated from 10 patients with Ph+ chronic phase CML on maintenance treatment with hydroxyurea. The cells were isolated by density gradient centrifugation followed by immunomagnetic depletion of leukemia and accessory cells. The ex vivo cytokine-producing capacity of CML T helper cells in response to polyclonal stimulation with anti-CD3 and anti-CD28 was then compared to that of cells purified from matched healthy volunteers. RESULTS: T helper cells purified from CML patients produced comparable amounts of the Th1 cytokines interleukin (IL)-2 and interferon (IFN)-g as cells purified from healthy volunteers. Likewise, no difference between CML and control T helper cells was found with respect to the Th2 cytokines, IL-4 and IL-13, as well as the immunomodulatory cytokine, IL-10. INTERPRETATION AND CONCLUSIONS: In the absence of leukemia and accessory cells, the intrinsic cytokine-producing capacity of CML T helper cells is normal. A Th2 shift was not detected, and the predominant presence of an IL-10-producing, immunosuppressive T helper cell subset could be excluded.