Johnson L L
Trudeau Institute, Inc., Saranac Lake, New York 12983.
Transplantation. 1991 Jun;51(6):1267-71. doi: 10.1097/00007890-199106000-00023.
The hypothesis was investigated that suppressor cells may be responsible for maintenance of immunologic tolerance of a minor H3 antigen in mice that express the antigen naturally. Lymphoid cell populations from B6.C-H-24c (HW54) mice, a congenic-resistant strain histoincompatible with H-24b-expressing C57BL/6 (B6) mice only with respect to the H-24 locus, were examined in cell-transfer experiments to see if they contained naturally arising H-24c-specific suppressor cells. The H-24 antigen was chosen for these studies because, unlike most other minor and major histocompatibility (H) antigens, it is not detectable on mature lymphoid cells by any of several functional criteria. Thus transfer of HW54 lymphoid cells to B6 hosts could be done without the complication of inducing hyporesponsiveness de novo in the host, as occurs with other minor H antigens that are expressed on lymphocytes. B6 hosts were given HW54 skin grafts along with HW54 lymphoid cells to assess their tolerance of the H-24c-encoded antigen. The hosts were either (1) normal, nonimmune B6 mice; (2) B6 mice rendered immunodeficient by thymectomy and irradiation (TXB) and repopulated with H-24c-immune B6 lymphocytes; or (3) TXB B6 hosts repopulated with nonimmune B6 lymphocytes. In each case it was found that the additionally infused HW54 lymphoid cells did not suppress the ability of these hosts to reject HW54 skin grafts. In other words, HW54 lymphoid cells appear not to possess suppressive activity specific for the H-24c antigen that might maintain antigen-specific natural tolerance. Additional experiments were performed to determine whether HW54 lymphoid cells can inhibit the ability of sublethally irradiated B6 mice to regain the capacity to reject HW54 skin. The purpose of these experiments was to determine whether there are naturally occurring HW54 lymphoid cells that can suppress the development of lymphocytes potentially reactive to H-24c antigen that presumably emerge in B6 mice following sublethal irradiation. Such suppressor cells would be candidate initiators of self-tolerance. Here, too, no evidence for such suppressor cells was obtained.
研究了一种假说，即抑制细胞可能负责维持在自然表达该抗原的小鼠中对次要H3抗原的免疫耐受。在细胞转移实验中，检测了B6.C-H-24c（HW54）小鼠的淋巴细胞群体，这是一种同基因抗性品系，仅在H-24位点与表达H-24b的C57BL/6（B6）小鼠组织不相容，以查看它们是否含有天然产生的H-24c特异性抑制细胞。选择H-24抗原进行这些研究，是因为与大多数其他次要和主要组织相容性（H）抗原不同，通过几种功能标准中的任何一种都无法在成熟淋巴细胞上检测到它。因此，将HW54淋巴细胞转移到B6宿主中时，不会像在淋巴细胞上表达的其他次要H抗原那样，引发宿主从头产生低反应性的并发症。给B6宿主移植HW54皮肤移植物以及HW54淋巴细胞，以评估它们对H-24c编码抗原的耐受性。宿主要么是（1）正常的、未免疫的B6小鼠；（2）通过胸腺切除术和照射（TXB）使其免疫缺陷并重新植入H-24c免疫的B6淋巴细胞的B6小鼠；要么是（3）重新植入未免疫B6淋巴细胞的TXB B6宿主。在每种情况下，都发现额外注入的HW54淋巴细胞并没有抑制这些宿主排斥HW54皮肤移植物的能力。换句话说，HW54淋巴细胞似乎不具有针对H-24c抗原的抑制活性，而这种活性可能维持抗原特异性的天然耐受性。进行了额外的实验，以确定HW54淋巴细胞是否能抑制经亚致死剂量照射的B6小鼠恢复排斥HW54皮肤的能力。这些实验的目的是确定是否存在天然存在的HW54淋巴细胞，它们可以抑制在亚致死剂量照射后可能出现在B6小鼠中的、对H-24c抗原有潜在反应性的淋巴细胞的发育。这样的抑制细胞将是自身耐受性的候选启动者。同样，在这里也没有获得这种抑制细胞的证据。
