Burkly L C, Degermann S, Longley J, Hagman J, Brinster R L, Lo D, Flavell R A
Biogen, Inc., Cambridge, MA 02142.
J Immunol. 1993 Oct 15;151(8):3954-60.
A variety of cell types expressing MHC class II molecules is known to function as APC in vitro. We employed the Ig kappa gene enhancer and promoter to target the class II E alpha gene, and thereby I-E, exclusively to B cells to address their APC function in vivo. Although transgenic I-E was expressed on B lymphocytes, we unexpectedly obtained I-E on thymic medullary epithelium but not macrophages and at low frequency on dendritic cells. Using these transgenic mice, we constructed bone marrow irradiation chimeras with I-E expressed only on medullary epithelium, in order to determine the role of this cell type in tolerance by clonal deletion in the thymus. Although it is accepted that bm-derived cells play a primary role in deletion, and thymic epithelium can delete clones to a lesser degree, the role of cortical vs medullary thymic epithelium has not been directly dissected. We demonstrate that medullary epithelium alone can tolerize by partial deletion of I-E-reactive V beta 5+ T cells. These results indicate a role for medullary epithelium in deletion during the later stages of thymic development, and support the notion that positive and negative selection of developing T cells can occur in distinct temporal and anatomic compartments.
已知多种表达MHC II类分子的细胞类型在体外可作为抗原呈递细胞（APC）发挥作用。我们利用免疫球蛋白κ基因增强子和启动子将II类Eα基因，进而将I-E基因特异性靶向B细胞，以研究其在体内的APC功能。尽管转基因I-E在B淋巴细胞上表达，但我们意外地在胸腺髓质上皮细胞上发现了I-E，而巨噬细胞上未发现，在树突状细胞上则以低频率表达。利用这些转基因小鼠，我们构建了仅在髓质上皮细胞上表达I-E的骨髓照射嵌合体，以确定这种细胞类型在胸腺中通过克隆清除实现免疫耐受中的作用。尽管人们普遍认为骨髓来源的细胞在克隆清除中起主要作用，胸腺上皮细胞在较小程度上也能清除克隆，但胸腺皮质与髓质上皮细胞的作用尚未得到直接剖析。我们证明，仅髓质上皮细胞就能通过部分清除I-E反应性Vβ5 + T细胞来诱导免疫耐受。这些结果表明髓质上皮细胞在胸腺发育后期的克隆清除中发挥作用，并支持这样一种观点，即发育中T细胞的阳性和阴性选择可在不同的时间和解剖区域发生。
