Role of CD28/B7 costimulation and IL-12/IL-10 interaction in the radiation-induced immune changes.
Role of CD28/B7 costimulation and IL-12/IL-10 interaction in the radiation-induced immune changes.
复制标题
DOI：
10.1186/1471-2172-2-8
复制
发表时间：
2001
期刊：
影响因子：
3
通讯作者：
Sun YM
中科院分区：
文献类型：
--
作者：
Liu SZ;Jin SZ;Liu XD;Sun YM
本文旨在研究B7/CD28相互作用及相关细胞因子的产生在不同剂量电离辐射后免疫学变化中的作用。研究发现，低剂量辐射 (LDR) 对淋巴细胞对 Con A 的增殖反应的刺激作用需要 APC 的存在。将从低剂量和高剂量照射的小鼠中获得的APC添加到从低剂量照射的小鼠中分离的脾淋巴细胞中，会刺激淋巴细胞增殖。 APC 上的 B7-1/2 表达在低剂量和高剂量辐射后均上调。 LDR后脾脏和胸腺淋巴细胞CD28表达上调，高剂量放射（HDR）后CD28表达受到抑制，细胞毒性T淋巴细胞相关抗原4（CTLA-4）表达呈相反方向变化。低剂量和高剂量辐射后，巨噬细胞的 IL-12 分泌均受到刺激，但脾细胞的 IL-10 合成受到低剂量辐射的抑制，而受到高剂量辐射的上调。在APC上存在上调的B7表达的情况下，T淋巴细胞上CD28/CTLA-4表达的状态决定了放射反应中免疫变化的结果，即LDR后CD28上调导致免疫增强，而HDR后与CD28下调相关的CTLA-4上调导致免疫抑制。低剂量和高剂量的辐射均上调 APC 上的 B7-1/2 表达。 LDR 后，APC 增加 IL-12 分泌的刺激增殖作用，通过抑制 IL-10 分泌而得到加强，进一步增强了 B7-CD28 相互作用诱导的细胞内信号传导。
The present paper aims at studying the role of B7/CD28 interaction and related cytokine production in the immunological changes after exposure to different doses of ionizing radiation. The stimulatory effect of low dose radiation (LDR) on the proliferative response of lymphocytes to Con A was found to require the presence of APCs. The addition of APCs obtained from both low- and high-dose-irradiated mice to splenic lymphocytes separated from low-dose-irradiated mice caused stimulation of lymphocyte proliferation. B7-1/2 expression on APCs was up-regulated after both low and high doses of radiation. There was up-regulation of CD28 expression on splenic and thymic lymphocytes after LDR and its suppression after high dose radiation (HDR), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression showed changes in the opposite direction. IL-12 secretion by macrophages was stimulated after both low and high doses of radiation, but IL-10 synthesis by splenocytes was suppressed by low dose radiation and up-regulated by high dose radiation. The status of CD28/CTLA-4 expression on T lymphocytes in the presence of up-regulated B7 expression on APCs determined the outcome of the immune changes in response to radiation, i.e., up-regulation of CD28 after LDR resulted in immunoenhancement, and up-regulation of CTLA-4 associated with down-regulation of CD28 after HDR led to immunosuppression. Both low and high doses of radiation up-regulated B7-1/2 expression on APCs. After LDR, the stimulated proliferative effect of increased IL-12 secretion by APCs, reinforced by the suppressed secretion of IL-10, further strengthened the intracellular signaling induced by B7-CD28 interaction.