Bashuda H, Takazawa K, Tamatani T, Miyasaka M, Yagita H, Okumura K
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
Transplantation. 1996 Jul 15;62(1):117-22. doi: 10.1097/00007890-199607150-00022.
We previously reported that a short course of treatment with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies (mAbs) led to a persistent acceptance of mouse cardiac allografts, which resulted from the induction of allospecific tolerance. In the present study, we tested the effect of anti-LFA-1 and anti-ICAM-1 mAbs on rat allograft rejection and analyzed the mechanisms underlying allograft tolerance. In sharp contrast to the mouse case, a short course of treatment with anti-LFA-1 and anti-ICAM-1 mAbs led to a persistent acceptance in only half of the treated rats when MHC was compatible but mismatched for minor antigens, and was virtually ineffective when MHC was fully incompatible. However, treatment with these mAbs combined with donor-specific transfusion and FK506 consistently led to a persistent acceptance, even when the MHC was fully incompatible. Donor-specific tolerance was induced by this treatment, as estimated by skin challenging. In the tolerant rats, proliferative response and CTL generation against donor-type alloantigen were severely impaired but partially restored by exogenous interleukin-2. Limiting dilution analysis demonstrated that the precursor frequency of CTL was decreased in the tolerant rats, as compared with the naive rats. These results suggest that donor-reactive T cells were partially deleted and rendered anergic in the periphery.
我们之前报道过，用抗LFA-1和抗ICAM-1单克隆抗体（mAb）进行短期治疗可导致小鼠心脏同种异体移植物的持续接受，这是同种异体特异性耐受诱导的结果。在本研究中，我们测试了抗LFA-1和抗ICAM-1 mAb对大鼠同种异体移植排斥反应的影响，并分析了同种异体移植耐受的潜在机制。与小鼠情况形成鲜明对比的是，当主要组织相容性复合体（MHC）相容但次要抗原不匹配时，用抗LFA-1和抗ICAM-1 mAb进行短期治疗仅导致一半接受治疗的大鼠持续接受移植物，而当MHC完全不相容时，该治疗实际上无效。然而，即使MHC完全不相容，用这些mAb联合供体特异性输血和FK506进行治疗也始终导致移植物的持续接受。通过皮肤挑战评估，这种治疗诱导了供体特异性耐受。在耐受的大鼠中，针对供体型同种异体抗原的增殖反应和细胞毒性T淋巴细胞（CTL）生成严重受损，但通过外源性白细胞介素-2可部分恢复。有限稀释分析表明，与未接触过抗原的大鼠相比，耐受大鼠中CTL的前体细胞频率降低。这些结果表明，供体反应性T细胞在外周部分被清除并变得无反应性。
