%0 Journal Article %T CD4+ T Cells are Exhausted and Show Functional Defects in Chronic Lymphocytic Leukemia %J Iranian Journal of Immunology %I Shiraz Institute for Cancer Research %Z 1735-1383 %A Allahmoradi, Esmaeil %A Taghiloo, Saeid %A Tehrani, Mohsen %A Hossein-Nattaj, Hadi %A Janbabaei, Ghasem %A Shekarriz, Ramin %A Asgarian-Omran, Hossein %D 2017 %\ 12/01/2017 %V 14 %N 4 %P 257-269 %! CD4+ T Cells are Exhausted and Show Functional Defects in Chronic Lymphocytic Leukemia %K Chronic lymphoblastic leukemia %K Exhausted CD4+ T Cell %K PD-1 %K Tim-3 %R %X Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become “exhausted” and characterized with poor effector functions and the expression of multiple inhibitory receptors. Objective: To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL. Methods: Peripheral blood mononuclear cells were obtained from 25 untreated CLL patients and 15 healthy volunteers. CLL patients were clinically classified according to the Rai staging system. The frequency of CD4+/Tim-3+/PD-1+ cells was obtained by flow cytometry. To evaluate cell proliferation and cytokine production, CD4+ T cells were isolated and stimulated with phytohemagglutinin and PMA/ionomycin. Concentrations of IL-2, IFN-γ, TNF-α, and IL-10 were measured in the culture supernatants of stimulated cells by the ELISA technique. Results: The percentage of CD4+/Tim-3+/PD-1+ cells was significantly higher in CLL patients than that of healthy controls. CD4+ T cells from CLL patients showed lower proliferative responses, a lower production of IL-2, IFN-γ, and TNF-α, and a higher production of IL-10, compared to healthy controls. CD4+ T cells from CLL patients in advanced clinical stages showed more exhaustion features than those of early stages. Conclusion: Given that the exhaustion phase of T cells can be reversible, targeted blocking of immune inhibitory molecules could be a promising tool to restore the host immune responses against leukemic cells in CLL. %U https://iji.sums.ac.ir/article_39322_9029a913c61823fbc825e875436c2f97.pdf