The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates
The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates
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DOI：
10.1016/s0022-5223(96)70101-0
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发表时间：
1996-10-01
影响因子：
6
通讯作者：
SuciuFoca, N
中科院分区：
文献类型：
--
作者：
Michler, RE;Shah, AS;SuciuFoca, N
在灵长类受者中，在作为同种异体移植的桥梁的一致性异种移植后，测定了对后续同种异体移植物的体液和细胞介导的免疫应答。从食蟹猴到ABH型匹配的橄榄狒狒进行异位心脏移植（n = 4），然后在2周内从ABH型匹配的狒狒供体进行同种异体移植。所有受者在异种移植时接受脾切除术，并接受环孢素、硫唑嘌呤和甲基强的松龙免疫抑制。这些灵长类动物的一致性异种移植不会诱导危及后续同种异体移植物的体液或细胞介导的免疫反应。异种特异性免疫反应性的程度，如通过来源于异种移植物的受体T细胞系的特异性细胞毒性和组织学异种移植物排斥的程度所确定的，不能预测随后同种异体移植物排斥的严重程度。在四个受体中的两个中，异种移植诱导了针对由来自一组12只无关狒狒的超过50%的成员的B细胞表达的抗原的同种异体反应性体液应答，在所有受者中，两个异种脾细胞的引发诱导了16%的同种异体淋巴细胞对加速的增殖性T细胞反应。这项研究肯定了协调异种移植物作为人类同种异体移植的适当生物桥梁的作用。然而，我们的研究结果表明，异种反应性狒狒记忆CD4 T细胞可以识别主要组织相容性复合物II类结构之间的异种和同种异体的目标。异种移植物诱导的潜在同种异体识别可能影响后续同种异体移植物供体选择的过程。
The humoral and cell-mediated immune responses to subsequent allografts were determined in primate recipients after concordant xenotransplantation as a bridge to allotransplantation. Heterotopic heart transplants (n = 4) were performed from cynomolgus monkeys into ABH type-matched olive baboons followed 2 weeks inter by allotransplantation from ABH type-matched baboon donors, Allografts were explanted at 8 weeks. All recipients underwent splenectomy at the time of xenotransplantation and received immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Concordant xenotransplantation in these primates did not induce humoral or cell-mediated immune responses that jeopardized subsequent allografts. The degree of xenospecific immune reactivity, as determined by specific cytotoxicity of recipient T-cell lines derived from the xenograft and extent of histologic xenograft rejection, did not predict the severity of subsequent allograft rejection, In two of the four recipients, xenotransplantation induced an alloreactive humoral response against antigens expressed by the B cells of more than 50% of members from a panel of 12 unrelated baboons, In all recipients, priming with xenogeneic splenocytes in two induced an accelerated proliferative T-cell response to allogeneic lymphocytes from 16% of this panel. This study affirms the role of concordant xenografts as appropriate biologic bridges to human allotransplantation. However, our results suggest that xenoreactive baboon memory CD4 T cells may recognize major histocompatibility complex class II-like structures shared between the xenogeneic and allogeneic targets. The potential allorecognition induced by a xenograft may affect the process of subsequent allograft donor selection.