The Inhibitor of Costimulation of T Cells: Abatacept
The Inhibitor of Costimulation of T Cells: Abatacept
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DOI：
10.3899/jrheum.120257
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发表时间：
2012-07-01
影响因子：
3.9
通讯作者：
Lapadula, Giovanni
中科院分区：
文献类型：
--
作者：
Iannone, Florenzo;Lapadula, Giovanni
Objective. T细胞共刺激是调节免疫耐受、免疫应答和自身免疫的关键点。T细胞活化不会发生在T细胞受体的简单接合上;需要第二个信号来完全刺激T细胞。有多种分子可以作为共刺激分子，其中CD 28/CD 80信号传导在调节T细胞应答中起着至关重要的作用。细胞毒性T淋巴细胞抗原-4（CD 152，CTLA 4）是CD 28的生理拮抗剂，并且阿巴西普（abatacept），CTLA 4的合成类似物，最近已被批准用于治疗类风湿性关节炎。异常的T细胞活化也被认为在皮肤和关节部位维持银屑病疾病。我们的目的是评估阻断CD 28/CD 80信号传导的基本原理和阿巴西普治疗银屑病关节炎（PsA）的可能用途。本文综述了CD 28/CD 80信号通路在银屑病T细胞炎症中的作用，以及CTLA 4在银屑病实验模型和人类中的调节作用。CD 28/CD 80似乎在刺激银屑病中的T细胞活化和炎症中是至关重要的，并且CTLA 4类似物或抗CD 28阻断抗体对其的抑制对银屑病有效。阿巴西普对银屑病A有一定的治疗价值，但对皮肤型银屑病的治疗作用不大。虽然CD 28分子在激活银屑病的T细胞和炎症中至关重要，但关于阿巴西普治疗PsA的疗效的数据仍然没有定论。（J Rheumol 2012;39 Suppl 89：100-2; doi：10.3899/jrheum.120257）
Objective. T cell costimulation is a key point in the regulation of immune tolerance, immune response, and autoimmunity. T cell activation does not take place upon the simple engagement of T cell receptor; a second signal is needed to fully stimulate T cells. There are a variety of molecules that can act as costimulators, and among those CD28/CD80 signaling plays a crucial role in modulating T cell response. Cytotoxic T lymphocyte antigen-4, CD152 (CTLA4) is a physiologic antagonist of CD28, and abatacept, a synthetic analog of CTLA4, has recently been approved to treat rheumatoid arthritis. An abnormal T cell activation is also believed to sustain psoriatic disease both at skin and joint sites. We aimed to evaluate the rationale of blocking CD28/CD80 signaling and the possible use of abatacept for treating psoriatic arthritis (PsA).Methods. We reviewed the role of CD28/CD80 signaling in promoting T cell inflammation in psoriasis and the effects of CTLA4 modulation in experimental models of psoriasis and in humans.Results. CD28/CD80 seems to be crucial in stimulating T cell activation and inflammation in psoriasis, and its inhibition by CTLA4 analogs or by anti-CD28 blocking antibodies is effective against psoriasis. Few data are available on abatacept, which seems to be valuable for the treatment of PsA but less useful in the therapy of skin psoriasis.Conclusion. Although the CD28 molecule is crucial in activating T cells and inflammation in psoriasis, data on the efficacy of abatacept in the treatment of PsA are still not conclusive. (J Rheumatol 2012;39 Suppl 89:100-2; doi:10.3899/jrheum.120257)