Oluwole S F, Reemtsma K, Hardy M A
Department of Surgery, Columbia University College of Physicians and Surgeons, New York 10032.
Transplantation. 1989 Jun;47(6):1001-7. doi: 10.1097/00007890-198906000-00017.
Lewis rats pretreated with UV-B-irradiated donor leukocytes (UV-DL) and peritransplant cyclosporine (CsA...CsA, 20 mg/kg on days 0, +1, and +2) accepted W/F heart allografts permanently. This study of donor-specific immunologic unresponsiveness and its cellular mechanisms shows that the induction phase of unresponsiveness is partially mediated by W3/25+ T cells, while its maintenance is dependent on the presence of 0 x 8+ T cells. In vivo adoptive transfer of either splenocytes, T lymphocytes (T cells), or W3/25+ T cells from ungrafted, UV-DL-transfused rats into unmodified syngeneic Lewis rats that received test grafts 24 hr later led to significant prolongation of donor-specific graft survival. Adoptive transfer of 0 x 8+ cells did not influence donor-type (W/F) test graft rejection. Adoptive transfer of SpL, T cells and 0 x 8+ cells from UV-DL and CsA-treated recipients of W/F heart allografts at 20 or 180 days after transplantation led to significant donor-specific graft prolongation in naive syngeneic hosts, while adoptive transfer of W3/25+ cells, in this group, did not affect test graft survival. However, the adoptive transfer of SpL or of T cell subsets did not influence third-party (ACI) graft survival. In-vitro mixed lymphocyte reaction between thoracic duct lymphocytes obtained at various intervals following grafting from UV-DL and CsA treated Lewis recipients of W/F heart allografts and donor-type SpL resulted in significantly reduced reactivity by 78%, 75%, 69% (P less than 0.001) and 43% (P less than 0.02) compared with controls when responder TDL were obtained at 20, 50, 100, and 180 days after transplantation, respectively. In coculture studies, the MLR response to donor SpL was specifically suppressed by 60%, 57%, 46%, and 50% (P less than 0.01) at 20, 50, 100, and 180 days after transplantation, respectively, compared with controls. These data indicate that the induction of specific unresponsiveness to heart allografts in this model is mediated, in part, initially by the appearance in the host of specific W3/25+ cells either induced or recalled by UV-DL transfusion, and that a stable state of immunologic unresponsiveness is subsequently dependent on the presence of 0 x 8+ suppressor cells.
用紫外线B照射的供体白细胞（UV-DL）和移植后环孢素（CsA……CsA，在第0天、+1天和+2天给予20mg/kg）预处理的Lewis大鼠永久性地接受了W/F心脏同种异体移植。这项关于供体特异性免疫无反应性及其细胞机制的研究表明，无反应性的诱导阶段部分由W3/25 + T细胞介导，而其维持依赖于0x8 + T细胞的存在。将未移植、接受UV-DL输血的大鼠的脾细胞、T淋巴细胞（T细胞）或W3/25 + T细胞体内过继转移到24小时后接受试验性移植的未修饰同基因Lewis大鼠中，导致供体特异性移植物存活时间显著延长。0x8 +细胞的过继转移不影响供体类型（W/F）试验性移植物的排斥反应。在移植后20天或180天，将UV-DL和CsA处理的W/F心脏同种异体移植受体的脾细胞、T细胞和0x8 +细胞过继转移到未接触过抗原的同基因宿主中，导致供体特异性移植物显著延长存活时间，而在该组中W3/25 +细胞的过继转移不影响试验性移植物存活。然而，脾细胞或T细胞亚群的过继转移不影响第三方（ACI）移植物存活。在移植后不同时间从UV-DL和CsA处理的W/F心脏同种异体移植的Lewis受体获得的胸导管淋巴细胞与供体类型的脾细胞之间的体外混合淋巴细胞反应显示，与对照组相比，当分别在移植后20天、50天、100天和180天获得反应性胸导管淋巴细胞时，反应性显著降低了78%、75%、69%（P<0.001）和43%（P<0.02）。在共培养研究中，与对照组相比，在移植后20天、50天、100天和180天，对供体脾细胞的混合淋巴细胞反应分别被特异性抑制了60%、57%、46%和50%（P<0.01）。这些数据表明，在该模型中，对心脏同种异体移植特异性无反应性的诱导部分最初是由UV-DL输血诱导或唤起的宿主中特异性W3/25 +细胞的出现介导的，并且免疫无反应性的稳定状态随后依赖于0x8 +抑制细胞的存在。
