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Frequency and functional characterization of exhausted CD 8 + T cells in chronic lymphocytic leukemia
Author(s) -
Taghiloo Saeid,
Allahmoradi Esmaeil,
Tehrani Mohsen,
HosseinNataj Hadi,
Shekarriz Ramin,
Janbabaei Ghasem,
Abediankenari Saeid,
AsgarianOmran Hossein
Publication year - 2017
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12880
Subject(s) - chronic lymphocytic leukemia , characterization (materials science) , leukemia , microbiology and biotechnology , cancer research , immunology , chemistry , medicine , biology , materials science , nanotechnology
Objectives The phenotypic and functional properties of Tim‐3 + / PD ‐1 + / CD 8 + cells as exhausted T cells were investigated in chronic lymphocytic leukemia ( CLL ). Methods Frequency of CD 8 + /Tim‐3 + / PD ‐1 + exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads‐isolated CD 8 + T cells were stimulated with PHA and PMA /ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA , respectively. Cytotoxic activity of isolated CD 8 + T cells was determined using CD 107a degranulation assay. Results The proportion of exhausted CD 8 + T cells was significantly higher in CLL compared to controls. Isolated CD 8 + T cells from CLL showed functional defects in proliferation, degranulation, and cytokines production. While IL ‐2, TNF ‐α, and IFN ‐γ were significantly lower in CLL patients, IL ‐10 was higher in the patients group. Patients with progressive clinical stages showed higher frequency and dysfunction of exhausted CD 8 + T cells. Conclusion Targeting immune inhibitory receptors to restore the function of tumor surrounding T cells could be helpful for immunotherapy of CLL .