CD4+ T Cells are Exhausted and Show Functional Defects in Chronic Lymphocytic Leukemia
<strong>Background:</strong> 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 “exh...
Main Authors: | , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Shiraz University of Medical Sciences
2017-12-01
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Series: | Iranian Journal of Immunology |
Subjects: | |
Online Access: | http://iji.sums.ac.ir/article_39322_9029a913c61823fbc825e875436c2f97.pdf |
Summary: | <strong>Background:</strong> 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. <strong>Objective:</strong> To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL. <strong>Methods:</strong> 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. <strong>Results:</strong> 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. <strong>Conclusion:</strong> 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. |
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ISSN: | 1735-1383 1735-367X |