Characterization of ectopic lymphoid structures in different types of acute renal allograft rejection

Summary

Background: We hypothesize that T cells such as IL-21+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 on 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.

Methods: 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 D (IgD), cell proliferation (Ki67), and double immunofluorescent stainings for IL-21 and BCL6 were performed.

Results: 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 mainly observed in aTCMRI biopsies.

Conclusion: ELSs with an activated phenotype are predominantly found in aTCMRI where T cells co-localize with B cells. These findings suggest a direct pathway of B cell allo-activation at the graft site during T cell mediated rejection. This article is protected by copyright. All rights reserved.