A radiosensitive APC activity dissociates IL-2 secretion and activation-induced cell death by autoreactive T cell hybridomas.
A radiosensitive APC activity dissociates IL-2 secretion and activation-induced cell death by autoreactive T cell hybridomas.
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放射敏感性 APC 活性可解离自身反应性 T 细胞杂交瘤的 IL-2 分泌和激活诱导的细胞死亡。
DOI：
10.1093/intimm/7.11.1787
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发表时间：
1995
影响因子：
4.4
通讯作者：
Gregerson,DS
中科院分区：
文献类型：
--
作者：
Prasad,SA;Fling,SP;Gregerson,DS
T细胞杂交瘤是从对牛视网膜S抗原的葡萄膜生成肽bov-B1具有特异性的LEW大鼠T细胞系产生的。使用这些自身反应性杂交瘤，IL-2产生和活化诱导的细胞死亡（AICD）被解离为活化的结果。自身反应性杂交瘤分泌IL-2，并进行AICD在响应于由未照射的同源脾细胞呈递的抗原，而由照射的脾细胞仅诱导AICD的抗原呈递。非自身反应性杂交瘤的IL-2产生不受APC照射的影响。用佛波酯或脂多糖和IL-4预处理APC可保护它们在γ射线照射后诱导IL-2分泌的能力。虽然共刺激阻断剂CTLA-4-IG通过阻止IL-2分泌而不是AICD来模拟γ-辐射的作用，但是APC上的B7表达不是辐射敏感的，与表达B7的第三方细胞“反式”提供的共刺激也不能重建抗原特异性杂交瘤IL-2分泌以响应辐射的APC。总之，数据显示，自身反应性T细胞杂交瘤的IL-2分泌和AICD可以在功能性共刺激信号存在下作为TCR占据的结果而解离。提出产生这些事件的信号仅通过TCR-⑶ 3复合物转导，并反映高亲和力和低亲和力相互作用的差异结果。
T cell hybridomas were generated from a LEW rat T cell line specific for the uveltogenic peptide bov-B1 of bovine retinal S-antigen. Using these autoreactive hybridomas, IL-2 production and activation-induced cell death (AICD) were dissociated as outcomes of activation. The self-reactive hybridomas secrete IL-2 and undergo AICD in response to antigen presented by non-irradiated syngeneic splenocytes, whereas antigen presentation by irradiated splenocytes induced only AICD. IL-2 production by a non-self reactive hybridoma was unaffected by irradiation of the APC. Pretreatment of the APC with phorbol ester or lipopolysaccharide and IL-4 protected their ability to induce IL-2 secretion after γ-irradiation. Although the co-stimulation-blocking reagent CTLA-4-Ig mimicked the effect of γ-irradiation by preventing IL-2 secretion but not AICD, B7 expression on the APC was not radiosensitive, nor did co-stimulation, provided‘in trans’with a B7-expressing thirdparty cell, reconstitute antigen-specific hybridoma IL-2 secretion in response to irradiated APC. In summary, the data show that IL-2 secretion and AICD of a self-reactive T cell hybridoma can be dissociated as consequences of TCR occupancy in the presence of a functional co-stimulatory signal. It is proposed that the signals producing these events are transduced through the TCR-CD3 complex alone and reflect the differential outcomes of high- and low-affinity interactions.