期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 14, 期 10, 页码 1088-1099出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2008.08.001
关键词
natural killer cells; regulatory T cells
资金
- National Institutes of Health [R01CA95327-02, R01CA102282-01A1, P20 RR016464]
- NATIONAL CANCER INSTITUTE [R01CA093527, R01CA102282] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR016464] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL056067] Funding Source: NIH RePORTER
Interleukin (IL)-2 has been extensively examined to promote clinical T and natural killer (NK) cell responses. Regulatory T cells (Tregs) have been shown to regulate many aspects of the immune system, including NK cell-mediated responses. We have demonstrated that in vivo administration of IL-2 led to activation and expansion of both NK cells and immunosuppressive Tregs. Therefore, we attempted to augment NK cell antitumor effects by concurrently depleting Tregs using anti-CD25. Increased NK cell activation by IL-2 was found to be correlated with an increase in classical, short-term NK cell in vitro killing assays regardless of the depletion of Tregs. But when splenocytes of the treated mice were used in long-term tumor outgrowth experiments, we observed that prior depletion of Tregs from IL-2 administration led to improved antitumor effects compared with either treatment alone. Importantly, these in vitro data are correlated with subsequent in vivo survival of leukemia-bearing mice, in which co-treatment of IL-2 with anti-CD25 led to significantly improved survival compared with mice treated with either IL-2 alone or with Treg depletion. Prior depletion of NK 1.1(+) cells, but not of CD8(+) cells, completely abrogated all antitumor effects mediated by IL-2 and anti-CD25 combination therapy. These findings demonstrate that superior INK cell-mediated anti-leukemic effects can be achieved with IL-2 administration and concurrent depletion of CD25(+) cells.
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