期刊
IMMUNOLOGY
卷 137, 期 3, 页码 249-258出版社
WILEY-BLACKWELL
DOI: 10.1111/imm.12004
关键词
arginase; granulocyte; immune suppression; myeloid derived suppressor cells; polymorphonuclear
类别
资金
- New Zealand Lotteries Grant Board
- Maurice & Phyllis Paykel Trust
- Bone Marrow Cancer Trust
- Cancer Society of NZ (Canterbury/Westland Division)
Human polymorphonuclear leucocytes (PMN) are thought to be immunosuppressive. The suppressive mechanism(s) used by PMN are, however, not well defined and in this study they were analysed using T-cell responses to CD3(+) CD28 monoclonal antibodies (mAb) as a readout. We demonstrate that in vitro activated PMN (PMNact) can, without any T-cell interaction, induce apparent T-cell suppression by inhibiting the stimulatory capacity of the CD3 mAb. However, a cell-directed suppression of T-cell proliferation was observed when PMNact were added to pre-activated T cells that are already committed to polyclonal proliferation. This suppression was partially reversed by catalase addition (P < 0.01) and largely reversed by addition of exogenous interleukin-2 (P < 0.001) but was not significantly reduced by nitric oxide synthase inhibition, myeloperoxidase inhibition or addition of excess arginine. Following removal of PMNact, suppressed T cells could respond normally to further stimulation. In addition to suppressing proliferation, co-culture with PMNact also induced a significant decrease in T-cell viability that was reversed by catalase addition (P < 0.05). The addition of the arginase inhibitor N-hydroxy-nor-l-arginine induced both a further significant, catalase-sensitive, loss in T-cell viability and increased nitrite release (P < 0.001). These data demonstrate that PMN, when activated, can both induce T-cell death and reversibly inhibit proliferation of activated T cells. The mechanisms underlying these distinct processes and the effects of arginase inhibitors on PMN induced cytotoxicity merit further investigation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据