ANTI-IDIOTYPIC NETWORK INDUCED BY T-CELL VACCINATION AGAINST EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

ANTI-IDIOTYPIC NETWORK INDUCED BY T-CELL VACCINATION AGAINST EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
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DOI:
10.1126/science.2447648
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发表时间:
1988-01-08
期刊:
影响因子:
56.9
通讯作者:
COHEN, IR
COHEN, IR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LIDER, O;RESHEF, T;COHEN, IR

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在对T细胞接种诱导的自身免疫性疾病的抵抗机制的研究中,通过在大鼠后足垫注射一次致脑炎剂量(104)的髓鞘碱性蛋白(BP)特异性T淋巴细胞克隆,对大鼠进行实验性自身免疫性脑脊髓炎(EAE)接种。通过用致脑炎剂量(3 × 1000)攻击大鼠来测定对接种的应答。106)BP特异性克隆的T淋巴细胞。接种后5 - 6天,负责介导过继转移EAE抗性的细胞集中在引流接种部位的腘淋巴结中。将引流淋巴结细胞转移至未接种疫苗的大鼠导致供体大鼠的抗性丧失和受体大鼠的抗性获得。用照射过的BP特异性克隆细胞作为刺激物建立引流淋巴结细胞的有限稀释培养物。从克隆中分离出两组对BP特异性T细胞特异性应答的T淋巴细胞:CD 4 + CD 8-辅助细胞和CD 4-CD 8+抑制细胞。辅助性T细胞,像BP抗原一样,特异性地刺激BP特异性接种克隆。相反,抑制性T细胞特异性抑制BP特异性接种克隆对其BP抗原的应答。这些结果表明,T细胞疫苗接种通过激活抗独特型网络诱导对自身免疫性疾病的抗性。
In a study of the mechanism of resistance to autoimmune disease induced by T cell vaccination, rats were vaccinated against experimental autoimmune encephalomyelitis (EAE) by injecting them once in the hind footpads with a subencephalitogenic dose (104) of a clone of T lymphocytes specific for myelin basic protein (BP). The response to vaccination was assayed by challenging the rats with an encephalitogenic dose (3 .times. 106) of T lymphocytes of this BP-specific clone. Five to six days after vaccination, the cells responsible for mediating resistance to adoptively transferred EAE were concentrated in the popliteal lymph nodes draining the vaccination site. Transfer of the draining lymph node cells to unvaccinated rats led to loss of resistance in the donor rats and acquisition of resistance by the recipient rats. Limiting-dilution cultures of the draining lymph node cells were established with irradiated cells of the BP-specific clone as stimulators. Two sets of T lymphocytes specifically responsive to the BP-specific T cells from the clone were isolated: CD4+CD8- helper and CD4-CD8+ suppressor cells. The helper T cells, like the BP antigen, specifically stimulated the BP- specific vaccinating clone. In contrast, the suppressor T cells specifically suppressed the response of the BP-specific vaccinating clone to its BP antigen. These results suggest that T cell vaccination induces resistance to autoimmune disease by activating an antiidiotypic network.