Feng J M, Givogri I M, Bongarzone E R, Campagnoni C, Jacobs E, Handley V W, Schonmann V, Campagnoni A T
Developmental Biology Group, Neuropsychiatric Institute, and Brain Research Institute, University of California Medical School, Los Angeles, CA 90024, USA.
J Immunol. 2000 Nov 15;165(10):5443-50. doi: 10.4049/jimmunol.165.10.5443.
The golli products of the myelin basic protein gene have been shown to be expressed in mouse thymus and brain. The full repertoire of thymic cell types expressing golli products has not yet been determined, although immunoreactivity has been found in some macrophages. We have analyzed the cellular expression of golli mRNAs and proteins in the thymus. The results showed that MTS5(+) cortical/MTS10(+) medullary epithelial cells and NLDC145(+) dendritic cells did not express golli, while some macrophages did exhibit strong immunoreactivity. GOLLI: mRNAs were not detected in macrophages by in situ hybridization. Thymocytes expressed significant levels of golli mRNAs and proteins by in situ hybridization and immunohistochemistry. Interestingly, golli immunoreactivity varied with thymocyte stage of differentiation. For example, CD4(-)CD8(-) (double-negative) thymocytes expressed relatively high levels of golli. Upon further differentiation into CD4(-)CD8(-) (double-positive) thymocytes, golli protein expression declined dramatically. When thymocytes developed into CD8(-) or CD4(+) (single-positive) thymocytes, golli protein expression increased again, but it never achieved the levels found in double-negative thymocytes. Thus, the altered levels of expression of golli proteins in developing thymocytes correlated with the transitions from double-negative to double-positive and double-positive to single-positive stages. The lack of significant golli expression in thymic stromal cells may offer an alternative explanation for the mechanism of inefficient negative selection of those autoreactive thymocytes with specificity for myelin basic proteins.
髓鞘碱性蛋白基因的golli产物已被证明在小鼠胸腺和大脑中表达。尽管在一些巨噬细胞中发现了免疫反应性,但表达golli产物的胸腺细胞类型的完整谱尚未确定。我们分析了胸腺中golli mRNA和蛋白质的细胞表达。结果表明,MTS5(+)皮质/MTS10(+)髓质上皮细胞和NLDC145(+)树突状细胞不表达golli,而一些巨噬细胞确实表现出强烈的免疫反应性。通过原位杂交在巨噬细胞中未检测到GOLLI mRNA。通过原位杂交和免疫组织化学,胸腺细胞表达了显著水平的golli mRNA和蛋白质。有趣的是,golli免疫反应性随胸腺细胞分化阶段而变化。例如,CD4(-)CD8(-)(双阴性)胸腺细胞表达相对高水平的golli。进一步分化为CD4(+)CD8(+)(双阳性)胸腺细胞后,golli蛋白表达急剧下降。当胸腺细胞发育为CD8(-)或CD4(+)(单阳性)胸腺细胞时,golli蛋白表达再次增加,但从未达到双阴性胸腺细胞中的水平。因此,发育中的胸腺细胞中golli蛋白表达水平的改变与从双阴性到双阳性以及从双阳性到单阳性阶段的转变相关。胸腺基质细胞中缺乏显著的golli表达可能为那些对髓鞘碱性蛋白具有特异性的自身反应性胸腺细胞阴性选择效率低下的机制提供另一种解释。