Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Am J Transplant. 2020 Sep;20(9):2551-2558. doi: 10.1111/ajt.15858. Epub 2020 May 4.
Alloreactive memory T cells play a key role in transplantation by accelerating allograft rejection and preventing tolerance induction. Some studies using µMT mice, which are constitutionally devoid of B cells, showed that B cells were required for the generation of memory T cells after allotransplantation. However, whether B cell depletion in normal adult mice has the same effect on memory responses by CD4 and CD8 T cells activated after transplantation has not been thoroughly investigated. In this study, we tested the effect of anti-CD20 antibody-mediated B cell depletion on CD4 and CD8 memory T cell alloresponses after skin transplantation in wild-type mice. We found that B cell depletion prevented the development of memory alloresponses by CD4 T cells but enhanced that of CD8 memory T cells. Next, we tested the influence of B cell depletion on hematopoietic chimerism. In OT-II CD4 anti-OVA TCR transgenic mice sensitized to ovalbumin antigen, B cell depletion also impaired allospecific memory T cell responses and thereby enhanced donor hematopoietic chimerism and T cell deletion after bone marrow transplantation. This study underscores the complexity of the relationships between B and T cells in the generation and reactivation of different memory T cell subsets after transplantation.
同种反应性记忆 T 细胞通过加速同种异体移植物排斥和防止诱导耐受在移植中发挥关键作用。一些使用 µMT 小鼠（其先天缺乏 B 细胞）的研究表明，在同种移植后，B 细胞对于记忆 T 细胞的产生是必需的。然而，在正常成年小鼠中耗尽 B 细胞是否对同种异体移植后激活的 CD4 和 CD8 T 细胞的记忆反应有相同的影响尚未得到彻底研究。在这项研究中，我们测试了抗 CD20 抗体介导的 B 细胞耗竭对野生型小鼠皮肤移植后 CD4 和 CD8 记忆 T 细胞同种反应的影响。我们发现 B 细胞耗竭可防止 CD4 T 细胞产生记忆同种反应，但增强 CD8 记忆 T 细胞的产生。接下来，我们测试了 B 细胞耗竭对造血嵌合体的影响。在对卵清蛋白抗原敏感的 OT-II CD4 抗 OVA TCR 转基因小鼠中，B 细胞耗竭也损害了同种特异性记忆 T 细胞反应，从而增强了骨髓移植后供体造血嵌合体和 T 细胞的缺失。这项研究强调了 B 细胞和 T 细胞在移植后不同记忆 T 细胞亚群的产生和再激活之间关系的复杂性。
