title: Normal intrinsic Th1/Th2 balance in patients with chronic phase chronic myeloid leukemia not treated with interferon-alpha or imatinib.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Dept. of Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. kiani@mk1.med.tu-dresden.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiani
authors.forename: Ivonne
authors.initials: I
authors.lastname: Habermann
authors.forename: Knut
authors.initials: K
authors.lastname: Schäke
authors.forename: Andreas
authors.initials: A
authors.lastname: Neubauer
authors.forename: Lars
authors.initials: L
authors.lastname: Rogge
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D016207:Cytokines / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016207:Cytokines; D004791:Enzyme Inhibitors; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D006918:Hydroxyurea