T cell lineages in the thymus of lpr/lpr mice. Evidence for parallel pathways of normal and abnormal T cell development.
T cell lineages in the thymus of lpr/lpr mice. Evidence for parallel pathways of normal and abnormal T cell development.
复制标题
lpr/lpr 小鼠胸腺中的 T 细胞谱系。
作者：
R. Budd;M. Schreyer;G. Miescher;H. Macdonald
lpr/lpr（lpr）基因纯合子的自身免疫小鼠由于外周淋巴组织中未成熟Thy-1+ Lyt-2-L3 T4-细胞的积累而发生严重的淋巴结病。这些细胞的来源尚不清楚，尽管胸腺的存在对于淋巴结肿大和自身免疫是必要的。由于这个原因以及异常lpr细胞表型与未成熟胸腺细胞相似的事实，我们研究了lpr小鼠的胸腺。发现成年lpr胸腺含有表型上与外周聚集细胞相同的未成熟群体，包括B220和Pgp-1抗原的表达以及由抗体KJ 16 -133定义的表面T细胞受体分子的存在。证据表明，这些lpr前体T细胞中的一些能够胸腺内分化，而绝大多数出口不变的淋巴结，其中一部分进一步分化成成熟的T细胞。通过表面表型和免疫组织学可以将lpr特异性谱系与lpr胸腺的正常组成部分区分开来。结果提示，lpr淋巴结中细胞的大量堆积与其说是T细胞异常增殖的结果，不如说是胸腺内分化异常的结果。此外，鉴定了正常Lyt-2-L3 T4-胸腺细胞的次要亚群，其类似于lpr细胞的表型并且类似地表达表面T细胞受体分子。因此，lpr胸腺中两个平行谱系的存在也提供了对正常T细胞发育的了解。
Autoimmune mice homozygous for the lpr/lpr (lpr) gene develop a profound lymphadenopathy resulting from the accumulation of immature Thy-1+ Lyt-2- L3T4- cells in peripheral lymphoid tissues. The source of these cells is not known although the presence of a thymus is necessary to manifest both the lymph node enlargement and the autoimmunity. For this reason and the fact that the abnormal lpr cell phenotypically resembles immature thymocytes, we studied the thymus in lpr mice. Adult lpr thymuses were found to contain an immature population phenotypically identical to the peripherally accumulating cells, including the expression of B220 and Pgp-1 antigens as well as the presence of surface T cell receptor molecules as defined by the antibody KJ16-133. Evidence is presented that some of these lpr precursor T cells are capable of intrathymic differentiation, whereas the vast majority are exported unchanged to the lymph nodes where a portion differentiate further into mature T cells. This lpr-specific lineage could be distinguished from a normal component of the lpr thymus by surface phenotype and immunohistology. The results suggest that the massive accumulation of cells in lpr lymph nodes is not so much the result of abnormal proliferation of T cells as abnormal intrathymic differentiation. In addition, a minor subpopulation of normal Lyt-2- L3T4- thymocytes was identified that resembles the phenotype of the lpr cell and similarly expresses surface T cell receptor molecules. The presence of two parallel lineages in the lpr thymus thus also provides insight into normal T cell development.