Immune Cell Infiltrate in Chronic-Active Antibody-Mediated Rejection

Background: Little is known about immune cell infiltrate type in the kidney allograft of patients with chronic-active antibody-mediated rejection (c-aABMR). Methods: In this study, multiplex immunofluorescent staining was performed on 20 cases of biopsy-proven c-aABMR. T-cell subsets (CD3, CD8, Foxp3, and granzyme B), macrophages (CD68 and CD163), B cells (CD20), and natural killer cells (CD57) were identified and counted in the glomeruli (cells/glomerulus) and the tubulointerstitial (TI) compartment [cells/high-power field (HPF)]. Results: In the glomerulus, T cells and macrophages were the dominant cell types with a mean of 5.5 CD3⁺ cells/glomerulus and 4 CD68⁺ cells/glomerulus. The majority of T cells was CD8⁺ (62%), and most macrophages were CD68⁺CD163⁺ (68%). The TI compartment showed a mean of 116 CD3⁺ cells/HPF, of which 54% were CD8⁺. Macrophage count was 21.5 cells/HPF with 39% CD68⁺CD163⁺. CD20⁺ cells were sporadically present in glomeruli, whereas B-cell aggregates in the TI compartment were frequently observed. Natural killer cells were rarely identified. Remarkably, increased numbers of CD3⁺FoxP3⁺ cells in the TI compartment were associated with decreased graft survival (p = 0.004). Conclusions: Renal allograft biopsies showing c-aABMR show a predominance of infiltrating CD8⁺ T cells, and increased numbers of interstitial FoxP3⁺ T cells are associated with inferior allograft survival.