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.
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 CMLpatients 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.
Authors: Abhishek A Mangaonkar; Kaaren K Reichard; Moritz Binder; Giacomo Coltro; Terra L Lasho; Ryan M Carr; April Chiu; Vivian Negron; Mehrdad Hefazi; Theodora Anagnostou; Michael M Timm; James W Hiebert; Jose C Villasboas; Wilson I Gonsalves; Naseema Gangat; Mithun Shah; Hassan B Alkhateeb; Aref Al-Kali; Michelle A Elliott; Kebede H Begna; Alexandra P Wolanskyj-Spinner; Mark R Litzow; William J Hogan; Stephen M Ansell; Animesh Pardanani; Ayalew Tefferi; Mrinal M Patnaik Journal: Blood Adv Date: 2020-11-10
Authors: Zuzana Humlová; Hana Klamová; Ivana Janatková; Karin Malíčková; Petra Králíková; Ivan Sterzl; Zdeněk Roth; Eva Hamšíková; Vladimír Vonka Journal: Clin Dev Immunol Date: 2010-12-12
Authors: Muneerah A H Huwaikem; Gauthaman Kalamegam; Ghadeer Alrefaei; Farid Ahmed; Roaa Kadam; Talal Qadah; Khalid H W Sait; Peter N Pushparaj Journal: Front Cell Dev Biol Date: 2021-03-18