Padberg W M, Kupiec-Weglinski J W, Lord R H, Araneda D H, Tilney N L
J Immunol. 1987 Jun 1;138(11):3669-74.
Cellular suppressor mechanisms developing during the induction of immunologic enhancement were studied in LEW rats immunized actively with BN spleen cells and passively with LEW anti-BN hyperimmune serum 11 and 10 days before receiving a (LEW X BN)F1 cardiac allograft, respectively. With this regimen, graft survival is prolonged from 7.4 +/- 0.5 days in unmodified, acutely rejecting hosts to 25 +/- 12 days in enhanced recipients, with one-third of the grafts surviving indefinitely. To test for suppressor capacities, 60 X 10(6) splenic T helper/inducer (W3/25+) and T suppressor/cytotoxic (OX8+) cells were adoptively transferred 7 and 14 days after transplantation either into unmodified syngeneic LEW animals that received (LEW X BN)F1 test grafts 24 hr later or into T cell-deprived B rats with indefinitely functioning heart transplants that were reconstituted with sensitized lymph node cells (100 X 10(6). W3/25+ T cells harvested on days 7 and 14 from enhanced recipients prolonged test graft survival in unmodified hosts (13.1 +/- 2.3 and 13.3 +/- 1.3 days, respectively, p less than 0.001) and delayed rejection in reconstituted B rats from 6.7 +/- 0.5 to 18.2 +/- 6.5 and 23.3 +/- 5.8 days, respectively (p less than 0.001). OX8+ and B lymphocytes had no suppressor activity. However, enzymatic stripping of the surfaces of W3/25+ cells abrogated suppressor function. Similarly, after i.p. treatment with cyclophosphamide, W3/25+ T cells lost their suppressor properties. Lack of donor specific but not third party alloaggressiveness was demonstrated by the profoundly diminished ability of W3/25+ lymphocytes from enhanced hosts to recreate rejection in nonreconstituted B rats, even when exogenous interleukin 2 was administered. After pronase treatment, however, W3/25+ T cells were capable of inducing immunoresponsiveness at a tempo similar to naive T helper cells (31.5 +/- 12.5 vs 32.8 +/- 7.9). Thus, the present studies provide evidence for the development of a specific W3/25+ suppressor cell in the induction of active and passive enhancement. Coincident abrogation of specific T effector alloaggressiveness is apparently mediated by surface-blocking factors.
在主动用BN脾细胞免疫且分别在接受（LEW×BN）F1心脏同种异体移植前11天和10天被动用LEW抗BN超免疫血清免疫的LEW大鼠中，研究了免疫增强诱导过程中产生的细胞抑制机制。采用这种方案，移植物存活时间从未经处理的急性排斥宿主中的7.4±0.5天延长至增强受体中的25±12天，三分之一的移植物无限期存活。为了测试抑制能力，在移植后7天和14天，将60×10⁶脾T辅助/诱导细胞（W3/25⁺）和T抑制/细胞毒性细胞（OX8⁺）过继转移到未经处理的同基因LEW动物中，这些动物在24小时后接受（LEW×BN）F1测试移植物，或者转移到T细胞缺失的B大鼠中，这些大鼠有无限期功能的心脏移植，并用致敏淋巴结细胞（100×10⁶）进行重建。从增强受体在第7天和第14天收获的W3/25⁺T细胞延长了未经处理宿主中测试移植物的存活时间（分别为13.1±2.3天和13.3±1.3天，p＜0.001），并将重建的B大鼠中的排斥反应从6.7±0.5天分别延迟至18.2±6.5天和23.3±5.8天（p＜0.001）。OX8⁺细胞和B淋巴细胞没有抑制活性。然而，用酶去除W3/25⁺细胞表面可消除抑制功能。同样，用环磷酰胺腹腔注射处理后，W3/25⁺T细胞失去其抑制特性。增强宿主的W3/25⁺淋巴细胞在未重建的B大鼠中重新引发排斥反应的能力显著降低，即使给予外源性白细胞介素-2，也证明缺乏供体特异性但不缺乏第三方同种异体攻击性。然而，在链霉蛋白酶处理后，W3/25⁺T细胞能够以与未致敏T辅助细胞相似的速度诱导免疫反应（31.5±12.5天对32.8±7.9天）。因此，本研究为在主动和被动增强诱导过程中特异性W3/25⁺抑制细胞的产生提供了证据。特异性T效应同种异体攻击性的同时消除显然是由表面阻断因子介导的。
