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CD4+ T Cells are Exhausted and Show Functional Defects in Chronic Lymphocytic Leukemia | ||
Iranian Journal of Immunology | ||
مقاله 1، دوره 14، شماره 4، اسفند 2017، صفحه 257-269 اصل مقاله (818.46 K) | ||
نوع مقاله: Original Article | ||
نویسندگان | ||
Esmaeil Allahmoradi1، 2؛ Saeid Taghiloo1، 2؛ Mohsen Tehrani1؛ Hadi Hossein-Nattaj1؛ Ghasem Janbabaei3؛ Ramin Shekarriz3؛ Hossein Asgarian-Omran* 1، 4 | ||
1Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences,Sari, Iran | ||
22 Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran | ||
3Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran | ||
4Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran | ||
چکیده | ||
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. | ||
کلیدواژهها | ||
Chronic lymphoblastic leukemia؛ Exhausted CD4+ T Cell؛ PD-1؛ Tim-3 | ||
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