Benham A m, Sawyer G J, Fabre J W
Division of Cell and Molecular Biology, Institute of Child Health, University of London, United Kingdom.
Transplantation. 1996 May 27;61(10):1455-60. doi: 10.1097/00007890-199605270-00007.
LEW rats with long-surviving (> 100 days) (DA x LEW)F1 kidney allografts were generated by treating the recipients with cyclosporine for 14 days after grafting. All rats were monitored after transplantation for the development of antibodies to intact donor class I MHC molecules. Cyclosporine completely suppressed the early antibody response to intact DA class I MHC molecules in all 19 LEW rats. However, 17 of the 19 rats developed antibodies between four and six weeks after grafting-i.e., between two and four weeks after the cessation of cyclosporine therapy, and maintained high levels of antibody to the donor class I molecules in spite of the long-term presence of the allograft. The 2 rats that did not produce antibodies to donor class I MHC molecules, along with one of the 17 that did produce antibodies, were immunized with a synthetic peptide corresponding to a region of the DA class I MHC molecule known to be recognized by LEW CD4+ T cells via the indirect recognition pathway. All 3 long survivors developed self APC-dependent CD4+ T cell proliferation to the immunizing donor peptides, and strong antibody responses to these peptides. However, none of these long survivors suffered rejection episodes as a consequence of the peptide immunization. In one of the two long-surviving rats without antibodies to intact donor class I MHC molecules at the time of peptide priming, the peptide priming resulted in the prompt development of strong antibodies to intact donor class I molecules. However, the other of these 2 rats did not produce such antibodies after peptide priming. Thus in this model of kidney allograft tolerance, with long-term exposure of the recipient's immune system to donor antigens without evidence of rejection, none of the animals develops tolerance for the indirect T cell recognition of donor class I MHC antigens. In occasional animals, B cells potentially reactive to intact donor class I molecules are present and are adequately exposed to antigen but are quiescent because of the absence of T cell help, perhaps as a consequence of reversible T cell suppression or anergy. In other occasional animals, B cell nonreactivity (anergy or tolerance) to intact donor class I molecules appears to develop.
通过在移植后用环孢素治疗受体14天，培育出具有长期存活（>100天）的（DA×LEW）F1肾同种异体移植的LEW大鼠。移植后对所有大鼠进行监测，以观察针对完整供体I类MHC分子的抗体的产生情况。环孢素完全抑制了所有19只LEW大鼠对完整DA I类MHC分子的早期抗体反应。然而，19只大鼠中有17只在移植后4至6周之间产生了抗体，即在停止环孢素治疗后的2至4周之间，并且尽管长期存在同种异体移植，但仍维持对供体I类分子的高水平抗体。未产生针对供体I类MHC分子抗体的2只大鼠，以及产生抗体的17只大鼠中的1只，用与已知可被LEW CD4 + T细胞通过间接识别途径识别的DA I类MHC分子区域相对应的合成肽进行免疫。所有3只长期存活者均产生了依赖自身抗原呈递细胞的CD4 + T细胞对免疫供体肽的增殖反应，以及对这些肽的强烈抗体反应。然而，这些长期存活者中没有一只因肽免疫而发生排斥反应。在肽激发时对完整供体I类MHC分子无抗体的两只长期存活大鼠中的一只，肽激发导致迅速产生针对完整供体I类分子的强抗体。然而，这2只大鼠中的另一只在肽激发后未产生此类抗体。因此，在这种肾同种异体移植耐受模型中，受体免疫系统长期暴露于供体抗原而无排斥迹象，但没有动物对供体I类MHC抗原的间接T细胞识别产生耐受。在偶尔的动物中，存在可能对完整供体I类分子有反应的B细胞，并且它们充分暴露于抗原，但由于缺乏T细胞帮助而处于静止状态，这可能是可逆性T细胞抑制或无反应性的结果。在其他偶尔的动物中，似乎会出现对完整供体I类分子的B细胞无反应性（无反应性或耐受性）。
