Intact CD100-CD72 Interaction Necessary for TCR-Induced T Cell Proliferation.
Intact CD100-CD72 Interaction Necessary for TCR-Induced T Cell Proliferation.
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DOI：
10.3389/fimmu.2017.00765
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发表时间：
2017
影响因子：
7.3
通讯作者：
Melum E
中科院分区：
文献类型：
--
作者：
Jiang X;Björkström NK;Melum E
通过抗体阻断来靶向 CD100 是一种潜在的癌症治疗策略，但很少考虑阻断这种免疫激活分子后对 T 细胞的功能影响。事实上，CD100 在 T 细胞中高表达，抗 CD100 抗体在 T 细胞增殖过程中发挥作用；然而，不同研究的结果有所不同，并且其潜在机制仍不清楚。为了解决这个问题，评估了针对 CD100 的单克隆抗体克隆。在珠结合的抗 CD3/CD28 存在的情况下，无论是在总外周血单核细胞还是纯化的 T 细胞培养系统中，其中四种抗体以可溶形式显着减少了 T 细胞的扩增。当用可溶性抗 CD72 而不是抗 CD100 抗体阻断 CD100-CD72 相互作用时，也观察到类似的抑制作用。相反，恢复 CD72-Fc 的相互作用消除了可溶性抗 CD100 诱导的抑制作用。总而言之，这些结果表明 T 细胞增殖是由 CD100 通过与 CD72 相互作用来调节的。他们进一步建立了体外系统来评估抗CD100抗体对T细胞的抑制作用，在临床试验中应注意这一点，以避免潜在的副作用。
Targeting CD100 by antibody blockade is a potential therapeutic strategy for cancers, but the functional effects on T cells following blockade of this immune activating molecule are rarely considered. Indeed, CD100 is highly expressed in T cells and anti-CD100 antibodies play a role during T cell proliferation; however, the outcome varies from different studies and the underlying mechanism is still unclear. To address this, monoclonal antibody clones directed against CD100 were evaluated. In their soluble form, four of these antibodies significantly reduced the expansion of T cells in the presence of bead-bound anti-CD3/CD28, either in total peripheral blood mononuclear cell or purified T cell culture systems. Similar inhibition was seen when blocking CD100–CD72 interaction by soluble anti-CD72 instead of anti-CD100 antibodies. Conversely, restoring the interaction by CD72-Fc eliminated the soluble anti-CD100-induced inhibitory effect. Taken together, these results reveal that T cell proliferation is regulated by CD100 via interaction with CD72. They further establish an in vitro system to evaluate the inhibitory effect of anti-CD100 antibodies on T cells, to which attention should be paid in clinical trials in order to avoid potential side effects.