期刊
MABS
卷 2, 期 1, 页码 35-41出版社
LANDES BIOSCIENCE
DOI: 10.4161/mabs.2.1.10561
关键词
chronic lymphocytic leukemia; IL-21; IL-2; immunosuppression; antibody dependent cellular cytotoxicity
资金
- National Cancer Institute [P01 CA95426]
- [T-32-5CA009338]
- NATIONAL CANCER INSTITUTE [P01CA095426, T32CA009338] Funding Source: NIH RePORTER
CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the novel common gamma chain cytokine interleukin (IL)-21 on primary B cells from CLL patients. Since members of this family of cytokines are known to exhibit their effects on diverse immune cells, we have examined the effects of IL-21 on CLL patient derived regulatory T cell (Treg) induction, expansion and the inhibitory effect on natural killer cells in vitro. We demonstrate here the expression of IL-21 receptor in CD4(+)CD25(High) regulatory cells from CLL patients. In contrast to IL-2, the IL-21 cytokine failed to mediate expansion of regulatory T cells or induced expression of Foxp3 in CD4+CD25(Intermediate) or CD4(+)CD25(Dim/-)T cells in whole blood derived from CLL patients. Interestingly, in contrast to their differential effects on expansion of the CD4(+)CD25 Foxp31cells, IL-2 and IL-21 exhibited a redundant role in Treg mediated suppression of NK cell mediated antibody dependent cytotoxicity function. Given the infusion related toxicities and pro-survival effect of IL-2 in CLL, these studies provide a rationale to explore IL-21 as an alternate gamma chain cytokine in CLL therapy.
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