Constitutive CD8 expression allows inefficient maturation of CD4+ helper T cells in class II major histocompatibility complex mutant mice.

Constitutive CD8 expression allows inefficient maturation of CD4+ helper T cells in class II major histocompatibility complex mutant mice.
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DOI:
10.1084/jem.179.6.1997
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发表时间:
1994-06-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Fowlkes BJ
Fowlkes BJ
中科院分区:
其他
文献类型:
--
作者:
Robey E;Itano A;Fanslow WC;Fowlkes BJ

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虽然成熟的CD 4 + T细胞携带识别II类主要组织相容性复合体(MHC)的T细胞受体(TCR),成熟的CD 8 + T细胞携带识别I类MHC的TCR,但可能未成熟胸腺细胞最初定型为CD 4或CD 8谱系而不考虑TCR的特异性。根据该模型,具有I类TCR的CD 4+细胞不会成熟,因为I类MHC识别和阳性选择需要CD 8辅助受体。如果这个模型是正确的,CD 8的组成型表达应该允许具有I类特异性TCR的CD 4 + T细胞发育。在这份报告中,我们表明,成熟的外周血CD 4+细胞存在于II类MHC缺陷的小鼠,表达组成性CD8.1转基因。这些细胞与主要的II类MHC选择的CD 4群体共享许多特性,包括在活化后表达CD 40配体的能力。尽管在II类MHC突变体/CD8.1转基因小鼠的胸腺中也可检测到成熟CD 4细胞,但它们代表了表达II类MHC的小鼠中发现的成熟CD 4细胞的一小部分。这些结果表明,一些T细胞选择的CD 4辅助谱系独立于其抗原受体特异性,然而,产生I类特异性CD 4细胞的效率低下,留下了开放的可能性,即在MHC识别产生的指导性信号可能会偏向谱系承诺。
Although mature CD4+ T cells bear T cell receptors (TCRs) that recognize class II major histocompatibility complex (MHC) and mature CD8+ T cells bear TCRs that recognize class I MHC, it is possible that the initial commitment of an immature thymocyte to a CD4 or CD8 lineage is made without regard to the specificity of the TCR. According to this model, CD4+ cells with class I TCR do not mature because the CD8 coreceptor is required for class I MHC recognition and positive selection. If this model is correct, constitutive expression of CD8 should allow CD4+ T cells with class I-specific TCRs to develop. In this report, we show that mature peripheral CD4+ cells are present in class II MHC-deficient mice that express a constitutive CD8.1 transgene. These cells share a number of properties with the major class II MHC-selected CD4 population, including the ability to express CD40 ligand upon activation. Although mature CD4 cells are also detectable in the thymus of class II MHC mutant/CD8.1 transgenic mice, they represent a small fraction of the mature CD4 cells found in mice that express class II MHC. These results indicate that some T cells choose the CD4 helper lineage independent of their antigen receptor specificity; however, the inefficiency of generating class I-specific CD4 cells leaves open the possibility that an instructive signal generated upon MHC recognition may bias lineage commitment.