Flynn J C, Conaway D H, Cobbold S, Waldmann H, Kong Y C
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Cell Immunol. 1989 Sep;122(2):377-90. doi: 10.1016/0008-8749(89)90085-3.
To delineate the contribution of L3T4+ and Lyt-2+ cells in the pathogenesis of experimental autoimmune thyroiditis (EAT), synergistic pairs of monoclonal antibodies (mAb) to the T cell subsets were used in conjunction with the adoptive transfer of mouse thyroglobulin (MTg)-activated cells from immunized mice. Initial experiments verified the important role of L3T4+ cells in the transfer of EAT. Subsequent experiments pointed to the relative contribution of both L3T4+ and Lyt-2+ cells, depending on the stage and extent of disease development. Treatment during disease with L3T4, but not Lyt-2, mAb alone significantly reduced thyroiditis. However, in situ analysis of the cellular infiltrate in thyroid sections revealed that, after treatment with mAb, the appropriate subset was eliminated without altering the amount of the other subset in the remaining lesion. In addition, treatment during severe thyroiditis following the transfer of MTg-activated lymph node cells showed that Lyt-2 mAb alone also reduced thyroid infiltration. When the recipients were pretreated with either pair of mAb before transfer, disease development was only moderately affected. We conclude that (i) donor L3T4+ cells are the primary cells responsible for the initial transfer and development of thyroiditis; and (ii) previous in vitro cytotoxicity data, plus current monoclonal antibody treatment of disease and in situ analysis, further implicate a role for Lyt-2+ cells in EAT pathogenesis.
为了阐明L3T4⁺和Lyt-2⁺细胞在实验性自身免疫性甲状腺炎（EAT）发病机制中的作用，将针对T细胞亚群的单克隆抗体（mAb）协同配对，与来自免疫小鼠的小鼠甲状腺球蛋白（MTg）激活细胞的过继转移联合使用。初步实验证实了L3T4⁺细胞在EAT转移中的重要作用。随后的实验指出了L3T4⁺和Lyt-2⁺细胞的相对作用，这取决于疾病发展的阶段和程度。在疾病期间单独用L3T4而不是Lyt-2单克隆抗体治疗可显著减轻甲状腺炎。然而，对甲状腺切片中细胞浸润的原位分析显示，在用单克隆抗体治疗后，适当的亚群被清除，而其余病变中另一个亚群的数量未改变。此外，在MTg激活的淋巴结细胞转移后严重甲状腺炎期间的治疗表明，单独使用Lyt-2单克隆抗体也可减少甲状腺浸润。当受体在转移前用任何一对单克隆抗体预处理时，疾病发展仅受到中度影响。我们得出结论：（i）供体L3T4⁺细胞是负责甲状腺炎初始转移和发展的主要细胞；（ii）先前的体外细胞毒性数据，加上目前对疾病的单克隆抗体治疗和原位分析，进一步表明Lyt-2⁺细胞在EAT发病机制中起作用。
