Generation of an inhibitory circuit involving CD8+ T cells, IL-2, and NK cell-derived TGF-beta: contrasting effects of anti-CD2 and anti-CD3.
Generation of an inhibitory circuit involving CD8+ T cells, IL-2, and NK cell-derived TGF-beta: contrasting effects of anti-CD2 and anti-CD3.
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DOI：
10.4049/jimmunol.160.5.2248
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发表时间：
1998-03
影响因子：
4.4
通讯作者：
J. Gray;M. Hirokawa;K. Ohtsuka;D. Horwitz
中科院分区：
文献类型：
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作者：
J. Gray;M. Hirokawa;K. Ohtsuka;D. Horwitz
虽然免疫抑制的现象是很好地建立了，在与下调活性的淋巴细胞的产生所涉及的机制知之甚少。与抗CD 3抗体不同，抗CD 2抗体的促有丝分裂组合不会刺激人PBL产生IgM或IgG。在确定这种差异的原因时，我们发现抗CD 2触发了由NK细胞提供的TGF-β促进的抑制回路。用抗-CD 2而不是抗-CD 3刺激PBL产生大量的活性TGF-β。发现NK细胞是TGF-β的重要来源，并且是组成性产生这种细胞因子的唯一淋巴细胞群体。抗-CD 2增强了纯化的NK细胞产生活性TGF-β。TGF-β去除NK细胞或加入抗TGF-β后，抗CD 2可刺激IG产生。抗TGF-β必须在前24小时内加入以获得最大效果。此外，CD 8 + T细胞短时间过夜暴露于TGF-β可以引发它们的抑制活性，前提是IL-2也存在。因此，与CD 8 + T细胞活化一致的活性TGF-β的存在可以调节这些细胞以介导下调活性，并且NK细胞可以充当该细胞因子的来源。
Although the phenomenon of immunosuppression is well established, the mechanisms involved in the generation of lymphocytes with down-regulatory activity are poorly understood. Unlike anti-CD3 antibodies, mitogenic combinations of anti-CD2 antibodies do not stimulate human PBL to produce IgM or IgG. In determining the reason for this difference, we have found that anti-CD2 triggers an inhibitory circuit facilitated by TGF-beta provided by NK cells. Stimulation of PBL with anti-CD2, but not anti-CD3, generated substantial amounts of active TGF-beta. NK cells were found to be a significant source of TGF-beta and were the only lymphocyte population that constitutively produced this cytokine. Anti-CD2 enhanced the production of active TGF-beta by purified NK cells. TGF-beta. After the removal of NK cells or the addition of anti-TGF-beta, anti-CD2 could stimulate Ig production. Anti-TGF-beta had to be added within the first 24 h for a maximal effect. Moreover, a short, overnight exposure of CD8+ T cells to TGF-beta could prime them for suppressor activity provided that IL-2 was also present. Thus, the presence of active TGF-beta coincident with CD8+ T cell activation can condition these cells to mediate down-regulatory activity, and NK cells can serve as the source of this cytokine.