CD4+ T cells anergized by high dose feeding establish oral tolerance to antibody responses when transferred in SCID and nude mice.
CD4+ T cells anergized by high dose feeding establish oral tolerance to antibody responses when transferred in SCID and nude mice.
复制标题
通过高剂量喂养激活的 CD4 T 细胞在转移到 SCID 和裸鼠中时建立了对抗体反应的口服耐受性。
作者：
K. Hirahara;T. Hisatsune;K. Nishijima;H. Kato;O. Shiho;S. Kaminogawa
以严重联合免疫缺陷（SCID）和BALB/c nu/nu小鼠为实验对象，通过细胞转移实验研究了口服耐受特异性抗体反应的细胞机制。高剂量给BALB/c小鼠喂牛α s1-酪蛋白（牛奶中的一种主要过敏原），可诱导对特异性Ab的口服特异性耐受。这种口服耐受状态成功地转移到具有口服耐受BALB/c小鼠脾细胞的SCID小鼠。在SCID小鼠中，在用α s1-酪蛋白免疫之前，用耐受性T细胞和正常B细胞转移，产生了对Ab反应的口服耐受性。此外，只有T细胞在裸鼠体内建立耐受状态。BALB/c小鼠脾T细胞对α s1-酪蛋白的增殖反应减弱，表明脾T细胞对α s1-酪蛋白的反应减弱是由于脾T细胞的无反应性。接下来，将耐受的脾T细胞进一步分离为CD4+ T细胞和CD8+ T细胞，与正常细胞混合，然后转移到裸鼠体内，发现裸鼠体内的耐受状态主要是由CD4+ T细胞产生的。当耐受CD4+ T细胞与正常CD4+ T细胞共转移到裸鼠体内时，特异性Ab反应没有明显降低。这些结果表明，经高剂量喂养的脾CD4+ T细胞在转移给SCID和裸鼠时，建立了对Ab反应的口服耐受。
The cellular mechanism for oral tolerance in specific Ab response was investigated by cell-transfer experiments, using severe combined immunodeficiency (SCID) and BALB/c nu/nu mice. High dose feeding with bovine alpha s1-casein, a major allergen in milk, to BALB/c mice induced Ag-specific oral tolerance to the specific Ab response. This state of oral tolerance was successfully transferred to SCID mice with splenocytes from orally tolerant BALB/c mice. In SCID mice that were transferred with tolerant T cells and normal B cells before being immunized with alpha s1-casein, oral tolerance to the Ab responses was generated. In addition, only the T cells established the tolerant state in nude mice. A decreased proliferative response of the splenic T cells from BALB/c mice against alpha s1-casein was also shown, indicating that the decreased Ab responses were attributed to the unresponsiveness of the splenic T cells. Next, the tolerant splenic T cells were further separated into CD4+ T cells and CD8+ T cells, remixed with normal cells, and then transferred to nude mice, which revealed that the tolerant state in the nude mice was principally generated by the CD4+ T cells. When tolerant CD4+ T cells were cotransferred with normal CD4+ T cells to nude mice, there was no significant reduction in the specific Ab responses. These results demonstrate that splenic CD4+ T cells anergized by high dose feeding established oral tolerance to the Ab responses when transferred to SCID and nude mice.