Section Transplantation and Nephrology, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Division of HPB and Transplant Surgery, Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands.
Clin Exp Immunol. 2018 May;192(2):224-232. doi: 10.1111/cei.13099. Epub 2018 Feb 2.
We hypothesize that T cells such as interleukin (IL)-21 B cell lymphoma 6 (BCL6) T follicular helper cells can regulate B cell-mediated immunity within the allograft during acute T cell-mediated rejection; this process may feed chronic allograft rejection in the long term. To investigate this mechanism, we determined the presence and activation status of organized T and B cells in so-called ectopic lymphoid structures (ELSs) in different types of acute renal allograft rejection. Biopsies showing the following primary diagnosis were included: acute/active antibody-mediated rejection, C4d (a/aABMR), acute T cell-mediated rejection grade I (aTCMRI) and acute T cell-mediated rejection grade II (aTCMRII). Paraffin sections were stained for T cells (CD3 and CD4), B cells (CD20), follicular dendritic cells (FDCs, CD23), activated B cells (CD79A), immunoglobulin (Ig)D, cell proliferation (Ki67) and double immunofluorescent stainings for IL-21 and BCL6 were performed. Infiltrates of T cells were detected in all biopsies. In aTCMRI, B cells formed aggregates surrounded by T cells. In these aggregates, FDCs, IgD and Ki67 were detected, suggesting the presence of ELSs. In contrast, a/aABMR and aTCMRII showed diffuse infiltrates of T and B cells but no FDCs and IgD. IL-21 was present in all biopsies. However, co-localization with BCL6 was observed mainly in aTCMRI biopsies. In conclusion, ELSs with an activated phenotype are found predominantly in aTCMRI where T cells co-localize with B cells. These findings suggest a direct pathway of B cell alloactivation at the graft site during T cell mediated rejection.
我们假设，白细胞介素（IL）-21+B 细胞淋巴瘤 6（BCL6）滤泡辅助 T 细胞等 T 细胞可以在急性 T 细胞介导的排斥反应期间调节移植物内的 B 细胞介导的免疫；这一过程可能在长期内导致慢性移植物排斥反应。为了研究这一机制，我们确定了不同类型的急性肾移植排斥反应中所谓异位淋巴样结构（ELSs）中组织化的 T 细胞和 B 细胞的存在和激活状态。纳入的活检标本具有以下主要诊断：急性/活跃抗体介导的排斥反应、C4d（a/aABMR）、急性 T 细胞介导的排斥反应 1 级（aTCMRI）和急性 T 细胞介导的排斥反应 2 级（aTCMRII）。石蜡切片分别对 T 细胞（CD3 和 CD4）、B 细胞（CD20）、滤泡树突状细胞（FDCs，CD23）、活化的 B 细胞（CD79A）、免疫球蛋白（Ig）D、细胞增殖（Ki67）和 IL-21 与 BCL6 的双免疫荧光染色进行染色。在所有活检标本中均检测到 T 细胞浸润。在 aTCMRI 中，B 细胞形成了由 T 细胞包围的聚集物。在这些聚集物中，检测到 FDCs、IgD 和 Ki67，表明存在 ELSs。相比之下，a/aABMR 和 aTCMRII 显示出弥漫性的 T 细胞和 B 细胞浸润，但没有 FDCs 和 IgD。所有活检标本中均存在 IL-21。然而，BCL6 的共定位主要在 aTCMRI 活检标本中观察到。总之，ELSs 具有激活表型，主要存在于 aTCMRI 中，其中 T 细胞与 B 细胞共定位。这些发现表明在 T 细胞介导的排斥反应期间，B 细胞在移植物部位发生直接的同种异体激活途径。
