GENETIC-CONTROL OF AUTOIMMUNE ENCEPHALOMYELITIS AND RECOGNITION OF THE CRITICAL NONAPEPTIDE MOIETY OF MYELIN BASIC-PROTEIN IN GUINEA-PIGS ARE EXERTED THROUGH INTERACTION OF LYMPHOCYTES AND MACROPHAGES

GENETIC-CONTROL OF AUTOIMMUNE ENCEPHALOMYELITIS AND RECOGNITION OF THE CRITICAL NONAPEPTIDE MOIETY OF MYELIN BASIC-PROTEIN IN GUINEA-PIGS ARE EXERTED THROUGH INTERACTION OF LYMPHOCYTES AND MACROPHAGES
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DOI:
10.1002/eji.1830110409
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发表时间:
1981-01-01
影响因子:
5.4
通讯作者:
COHEN, IR
COHEN, IR
中科院分区:
医学3区
文献类型:
--
作者:
BENNUN, A;OTMY, H;COHEN, IR

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研究了对实验性自身免疫性脑脊髓炎(EAE)耐药或易感的近交系豚鼠对髓鞘碱性蛋白(BP)致脑性非肽(NP)决定因子的遗传控制。对骨髓重建动物的研究表明,EAE诱导的易感性是淋巴造血系统细胞基因型的功能,而不是生理环境或靶器官的功能。T细胞反应分析表明,易感菌株13 ~ 2倍。13) F1杂交豚鼠在注射全BP[完全弗氏]佐剂时识别NP决定因素。耐药菌株2豚鼠对BP上未定义的决定因素有反应,但对NP部分没有反应。通过给敏感的F1杂交种注射两种亲本菌株的bp脉冲巨噬细胞,研究了参与调节NP决定因子反应的细胞。敏感株13巨噬细胞触发对NP决定因子的应答,诱导临床EAE。注射了耐药株2巨噬细胞的F1动物对NP决定因素没有反应,尽管巨噬细胞能够呈现整个BP中存在的其他未定义决定因素。显然,NP决定性免疫反应的遗传控制是在巨噬细胞向T淋巴细胞的抗原呈递水平上发挥作用的。
Genetic control was studied in the response to the encephalitogenic nonapeptide (NP) determinant of myelin basic protein (BP) in inbred guinea pigs of strains resistant or susceptible to induction of experimental autoimmune encephalomyelitis (EAE). Studying bone marrow-reconstituted animals showed that suceptibility to EAE induction was a function of the genotype of the cells of the lymphohematopoietic system and not of the physiological environment or target organ. Analysis of the T cell response showed that susceptible strain 13 or (2 .times. 13) F1 hybrid guinea pigs recognized the NP determinant when injected with whole BP in [complete Freund''s] adjuvant. Resistant strain 2 guinea pigs responded to undefined determinants on BP, but not to the NP moiety. The cells involved in regulating the response to the NP determinant were studied by injecting susceptible F1 hybrids with BP-pulsed macrophages of either parental strain. Susceptible strain 13 macrophages triggered a response to the NP determinant and induced clinical EAE. F1 animals injected with resistant strain 2 macrophages failed to respond to the NP determinant, although the macrophages were capable of presenting other undefined determinants present on whole BP. Apparently, genetic control of the NP determinant immune response is exerted at the level of antigen presentation by macrophages to T lymphocytes.