Hori S, Sato S, Kitagawa S, Azuma T, Kokudo S, Hamaoka T, Fujiwara H
Biomedical Research Center, Osaka University Medical School, Japan.
J Immunol. 1989 Sep 1;143(5):1447-52.
The present study investigates the effects of i.v. presensitization with class II H-2-disparate allogeneic cells on various L3T4+ T cell functions including the capability of rejecting the corresponding allogeneic skin graft. C57BL/6 (B6) mice were i.v. presensitized with class II H-2 disparate B6-C-H-2bm12 (bm12) spleen cells. Such presensitization did not affect the bm12-specific L3T4+ T cell-mediated proliferative and interleukin 2 (IL-2)-producing capacities. A single cell suspension of (B6 x bm12)F1 spleen cells was depleted of APC by two round-passages over Sephadex G-10 columns. This APC-depleted fraction of (B6 x bm12)F1 cells failed to stimulate B6 responding cells in mixed lymphocyte reactions (MLR). The addition of recombinant IL-1 to the MLR restored anti-bm12 MLR responses, indicating that APC-depleted (B6 x bm12)F1 cells bear bm12 alloantigens but are unable to stimulate B6 anti-bm12 L3T4+ T cells. A single i.v. administration of APC-depleted (B6 x bm12)F1 cells into B6 mice resulted in almost complete abrogation of the capacity of recipient B6 lymphoid cells to give anti-bm12 MLR and IL2 production. This suppression was bm12 alloantigen-specific and attributed to the elimination or functional impairment of anti-bm12 T cell clones rather than the induction of suppressor cells. The tolerance was also observed in graft-rejection responses. The strikingly prolonged survival of bm12 skin grafts was produced when grafts were implanted into B6 mice which had been presensitized with APC-depleted, but not with untreated (B6 x bm12)F1 spleen cells. These results indicate that allo-class II H-2 antigen-reactive L3T4+ T cells are rendered tolerant by i.v. presensitization with APC-depleted fraction of the corresponding allogeneic cells.
本研究调查了用II类H-2不相合的同种异体细胞进行静脉预致敏对各种L3T4+ T细胞功能的影响，包括排斥相应同种异体皮肤移植的能力。用II类H-2不相合的B6-C-H-2bm12（bm12）脾细胞对C57BL/6（B6）小鼠进行静脉预致敏。这种预致敏不影响bm12特异性L3T4+ T细胞介导的增殖能力和白细胞介素2（IL-2）产生能力。通过在Sephadex G-10柱上进行两轮传代，去除（B6×bm12）F1脾细胞的单细胞悬液中的抗原呈递细胞（APC）。这种去除APC的（B6×bm12）F1细胞部分在混合淋巴细胞反应（MLR）中未能刺激B6应答细胞。向MLR中添加重组IL-1可恢复抗bm12 MLR反应，表明去除APC的（B6×bm12）F1细胞携带bm12同种异体抗原，但无法刺激B6抗bm12 L3T4+ T细胞。将去除APC的（B6×bm12）F1细胞静脉内单次注射到B6小鼠体内，导致受体B6淋巴细胞产生抗bm12 MLR和IL-2的能力几乎完全丧失。这种抑制是bm12同种异体抗原特异性的，归因于抗bm12 T细胞克隆的消除或功能受损，而不是抑制细胞的诱导。在移植排斥反应中也观察到了耐受性。当将bm12皮肤移植到用去除APC的（B6×bm12）F1脾细胞（而非未处理的（B6×bm12）F1脾细胞）预致敏的B6小鼠体内时，移植皮肤的存活时间显著延长。这些结果表明，通过用相应同种异体细胞去除APC的部分进行静脉预致敏，可使同种II类H-2抗原反应性L3T4+ T细胞产生耐受性。
