B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation.
B Cell Depletion With an Anti-CD20 Antibody Enhances Alloreactive Memory T Cell Responses After Transplantation.
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DOI：
10.1111/ajt.13483
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Benichou G
中科院分区：
文献类型：
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作者：
Marino J;Paster JT;Trowell A;Maxwell L;Briggs KH;Crosby Bertorini P;Benichou G
同种异体记忆T细胞介导加速同种异体移植排斥和移植耐受抵抗。最近的研究表明，B细胞缺陷小鼠在移植后不能产生供体特异性记忆T细胞反应。同时，其他研究表明，移植前使用利妥昔单抗（IgG1 anti-CD20 mAb）联合环孢素A清除B细胞可促进猴子胰岛异体移植物的存活。在这项研究中，我们研究了抗cd20抗体介导的B细胞耗竭对小鼠记忆性T细胞同种异体反应的影响。用IgG2a抗cd20单克隆抗体处理野生型和抗ova TCR转基因小鼠，几乎耗尽了外周血和次级淋巴器官中的所有B细胞，但保留了骨髓中的一些B细胞。B细胞耗竭不影响naïve小鼠皮肤移植后的直接同种异体反应，但导致间接同种异体反应显著增加。此外，在同种异体致敏小鼠中，抗cd20单抗治疗增强了同种异体记忆T细胞的再激活，加速了同种异体皮肤移植物的第二次排斥反应。这表明抗cd20抗体对同种异体免疫和同种异体移植排斥反应的影响可能因抗体的性质以及它们递送的环境而异。
Alloreactive memory T cells mediate accelerated allograft rejection and transplant tolerance resistance. Recent studies have shown that B cell deficient–µMT mice fail to mount donor-specific memory T cell responses after transplantation. At the same time, other studies showed that pretransplant B cell depletion using rituximab (IgG1 anti-CD20 mAb) combined with cyclosporine A promoted the survival of islet allografts in monkeys. In this study, we investigated the effect of anti-CD20 antibody-mediated B cell depletion on the memory T cell alloresponse in mice. Wild-type and anti-OVA TCR transgenic mice were treated with an IgG2a anti-CD20 monoclonal antibody, which depleted nearly all B cells in the peripheral blood and secondary lymphoid organs but spared some B cells in the bone marrow. B cell depletion did not affect the direct alloresponse but resulted in a marked increase of indirect alloresponse after skin transplantation of naïve mice. Furthermore, in allosensitized mice, anti-CD20 mAb treatment enhanced the reactivation of allospecific memory T cells and accelerated second set rejection of skin allografts. This suggests that the effect of anti-CD20 antibodies on alloimmunity and allograft rejection might vary upon the nature of the antibodies as well as the circumstances under which they are delivered.