Inhibition of IL‐2 production by nitric oxide: A novel self‐regulatory mechanism for Th1 cell proliferation
Inhibition of IL‐2 production by nitric oxide: A novel self‐regulatory mechanism for Th1 cell proliferation
复制标题
一氧化氮抑制 IL-2 产生：Th1 细胞增殖的新型自我调节机制
作者：
A. Taylor
克隆的Th 1细胞，而不是Th 2细胞，对疟疾抗原特异性，产生一氧化氮（NO）时，与特异性抗原或刀豆蛋白A激活。此外。NO抑制Th 1细胞的增殖以及Th 2细胞产生IL-2和IFN-γ，但不抑制Th 2细胞的增殖和产生IL-2和IFN-γ。在此，证明了NO供体S-亚硝基-N-乙酰青霉胺（SNAP）对Th 1细胞增殖的抑制可以通过添加rIL-2而不是rIFN-γ来逆转，这表明NO对Th 1细胞的抑制可能呈现IL-2的产生。剂量反应研究表明，当在体外用相对低浓度的抗原或有丝分裂原刺激时，Th 1细胞产生最佳水平的IL-2和增殖反应，并且没有检测到NO。然而，随着抗原/有丝分裂原的增加，产生了高水平的NO，伴随着IL-2分泌和T细胞增殖的减少。SNAP可类似地抑制体外用Con A活化的正常脾的初始CD 4 + T细胞的增殖和IL-2-IFN-γ的产生。这些结果表明，NO可能作为一种自我调节分子，防止Th 1细胞过度扩增。不受限制的Th 1细胞活性与一系列免疫病理学和自身免疫性疾病有关。Th 1细胞功能下调的拟议机制也可以解释疟疾感染中观察到的淋巴细胞增殖抑制。
Cloned Th1 cells, but not Th2 cells, specific for malaria antigen, produce nitric oxide (NO) when activated with specific antigen or Con A. Furthermore. NO inhibits proliferation of, and production of IL‐2 and IFN‐γ by, Th1 but not Th2 cells, Here, it is demonstrated that the inhibition of Th1 cell proliferation by the NO donor S‐nitroso‐N‐acetyl penicillamine (SNAP) can be reversed by the addition of rIL‐2 but not of rIFN‐γ, suggesting that the inhibition of Th1 cells by NO may be presenting the production of IL‐2. Dose‐response studies showed that Th1 cells produce optimal levels of IL‐2 and a proliferative response, and no detectable NO, when stimulated with relatively low concentrations of antigen or mitogen in vitro. As the antigen/mitogen increased, however, high levels of NO were produced, accompanied by a concomitant reduction in IL‐2 secretion and T cell proliferation. The proliferation of, and IL‐2‐IFN‐γ production by, naive CD4+ T cells from normal spleens activated with Con A in vitro can be similarly inhibited by SNAP. These results suggest that NO may serve as a self‐regulator molecule preventing the over‐expansion of Th1 cells. Unrestricted Th1 cell activity has been implicated in a range of immunopathologies and autoimmune diseases. The proposed mechanism for down‐regulation of Th1 cell function may also account for the suppression of lymphocyte proliferation observed in malaria infections.
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影响因子：
4.4
作者：
D. Stuehr;M. Marletta
通讯作者：
D. Stuehr;M. Marletta
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
DOI：
10.1073/pnas.84.18.6369
发表时间：
1987-09-01
影响因子：
11.1
作者：
IYENGAR, R;STUEHR, DJ;MARLETTA, MA
通讯作者：
MARLETTA, MA
DOI：
10.1016/s0021-9258(17)36703-0
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
C. Nathan;Q. Xie
通讯作者：
C. Nathan;Q. Xie
影响因子：
4.4
作者：
J. Albina;J. Abate;W. Henry
通讯作者：
J. Albina;J. Abate;W. Henry