期刊
BLOOD
卷 121, 期 9, 页码 1612-1621出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-09-457531
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资金
- CR-UK
- European Hematology Association
- MRC
- National Cancer Institute [P01 CA95426]
- Goldman Sachs
- MRC [G0902269] Funding Source: UKRI
- Medical Research Council [G0902269] Funding Source: researchfish
T-cell exhaustion, originally described in chronic viral infections, was recently reported in solid and hematologic cancers. It is not defined whether exhaustion contributes to T-cell dysfunction observed in chronic lymphocytic leukemia (CLL). We investigated the phenotype and function of T cells from CLL patients and age-matched controls. CD8(+) and CD4(+) T cells from CLL patients had increased expression of exhaustion markers CD244, CD160, and PD1, with expansion of a PD1(+)BLIMP1(HI) subset. These molecules were most highly expressed in the expanded population of effector T cells in CLL. CLL CD8(+) T cells showed functional defects in proliferation and cytotoxicity, with the cytolytic defect caused by impaired granzyme packaging into vesicles and nonpolarized degranulation. In contrast to virally induced exhaustion, CLL T cells showed increased production of interferon-gamma and TNF alpha and increased expression of TBET, and normal IL2 production. These defects were not restricted to expanded populations of cytomegalovirus (CMV)-specific cells, although CMV seropositivity modulated the distribution of lymphocyte subsets, the functional defects were present irrespective of CMV serostatus. Therefore, although CLL CD8(+) T cells exhibit features of T-cell exhaustion, they retain the ability to produce cytokines. These findings also exclude CMV as the sole cause of T-cell defects in CLL.
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