ELIMINATION OF CD8+ THYMOCYTES IN TRANSGENIC MICE EXPRESSING AN ANTI-LYT2.2 IMMUNOGLOBULIN HEAVY-CHAIN GENE

ELIMINATION OF CD8+ THYMOCYTES IN TRANSGENIC MICE EXPRESSING AN ANTI-LYT2.2 IMMUNOGLOBULIN HEAVY-CHAIN GENE
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DOI:
10.1002/j.1460-2075.1989.tb08547.x
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发表时间:
1989-12-01
期刊:
影响因子:
11.4
通讯作者:
EIBEL, H
EIBEL, H
中科院分区:
生物学1区
文献类型:
--
作者:
BROMBACHER, F;LAMERS, MC;EIBEL, H

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单个T细胞群体的特征在于特异性表面蛋白,即T细胞受体复合物(TCR)和两种辅助分子,CD 8(Lyt 2)和CD 4(L3 T4)。CD 8和CD 4是T细胞与I类或II类主要组织相容性复合体分子相互作用所必需的。在胸腺中,未成熟的CD 8 + 4- TCR-细胞可能通过短阶段的CD 8 + 4-胸腺细胞分化为CD 8 +4+ TCR+ T细胞,并进一步成熟为主要的T细胞群,即CD 8 +4- TCR+细胞毒性T淋巴细胞和CD 4 +8- TCR+ T辅助细胞。为了分析涉及CD 8的分化步骤,我们产生了表达μ C的转基因小鼠。来自抗Lyt2.2杂交瘤的重链基因。表达完整的(. mu.sm)或仅表达分泌的μ蛋白(μ s)遭受其CD 8 +4+胸腺细胞的严重消耗,也影响成熟的CD 8 +4-和CD 4 +8-群体。所述消耗与转基因μ-胸腺细胞内的链蛋白。这种胸腺细胞内的μ细胞表达,链阻止CD 8 -4-胸腺细胞进一步分化,最可能是通过μ-胸腺细胞之间的细胞内相互作用。重链和CD 8蛋白。这些结果表明,CD 8在胸腺细胞成熟过程中起重要作用。
Individual T cell populations are characterized by specific surface proteins, namely by the T cell receptor complex (TCR) and by two accessory molecules, CD8 (Lyt2) and CD4 (L3T4). CD8 and CD4 are required for T cell interactions with class I or class II major histocompatibility complex molecules. In the thymus, immature CD8-4- TCR- cells differentiate, possibly via a short stage of CD8+ 4- thymocytes, into CD8+4+ TCR+ T cells and mature further into the main T cell populations, the CD8+4- TCR+ cytotoxic T lymphocytes and the CD4+8- TCR+ T helper cells. In order to analyse the differentiation steps involving CD8, we generated transgenic mice expressing .mu. heavy chain genes from an anti-Lyt2.2 hybridoma. Transgenic lines expressing either the complete (.mu.sm) or only the secreted .mu. protein (.mu.s) suffer from a severe depletion of their CD8+4+ thymocytes affecting also the mature CD8+4- and CD4+8- populations. The depletion is correlated to the expression of transgenic .mu.-chain proteins within thymocytes. This intrathymocyte expression of the .mu. chain prevents CD8-4- thymocytes from further differentiation, most probably via intracellular interactions between .mu. heavy chain and CD8 proteins. These results show that CD8 plays in important role during thymocyte maturation.