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Review
. 2024 Dec 11:37:13835.
doi: 10.3389/ti.2024.13835. eCollection 2024.

Deciphering the Complexity of the Immune Cell Landscape in Kidney Allograft Rejection

George Terinte-Balcan  1   2   3 , Emilie Lebraud  3 , Julien Zuber  4 , Dany Anglicheau  3   4 , Gener Ismail  1   5 , Marion Rabant  2   3
Affiliations
Review

Deciphering the Complexity of the Immune Cell Landscape in Kidney Allograft Rejection

George Terinte-Balcan et al. Transpl Int. .

Abstract

While the Banff classification dichotomizes kidney allograft rejection based on the localization of the cells in the different compartments of the cortical kidney tissue [schematically interstitium for T cell mediated rejection (TCMR) and glomerular and peritubular capillaries for antibody-mediated rejection (AMR)], there is a growing evidences that subtyping the immune cells can help refine prognosis prediction and treatment tailoring, based on a better understanding of the pathophysiology of kidney allograft rejection. In the last few years, multiplex IF techniques and automatic counting systems as well as transcriptomics studies (bulk, single-cell and spatial techniques) have provided invaluable clues to further decipher the complex puzzle of rejection. In this review, we aim to better describe the inflammatory infiltrates that occur during the course of kidney transplant rejection (active AMR, chronic active AMR and acute and chronic active TCMR). We also discuss minor components of the inflammatory response (mastocytes, eosinophils, neutrophils, follicular dendritic cells). We conclude by discussing whether the over simplistic dichotomy between AMR and TCMR, currently used in clinical routine, remains relevant given the great diversity of immune actors involved in rejections.

Keywords: complexity; heterogeneity; immune cells; infiltrates; rejection.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Multiplex immunofluorescence image highlighting the diversity of immune cells involved in kidney allograft rejection. Endothelial cells are stained with an anti CD34 antibody (green), B lymphocytes by an anti CD20 antibody (yellow), T lymphocytes using an anti CD3 antibody (turquoise), macrophages using an anti CD68 antibody (purple) and NK cells using an anti NkP46 antibody (orange). DAPI (blue) stains for cell nuclei. (A) illustrates a T cell mediated rejection, (B) illustrates an antibody mediated rejection.
FIGURE 2
FIGURE 2
Heterogeneity of the composition of the inflammatory infiltrate during TCMR and AMR (from [19]). During both AMR and TCMR, biopsies displayed a wide range of proportions of the main inflammatory cells (CD3+ T lymphocytes, and CD163+ macrophages), and a small proportion of NkP46+ NK cells.
FIGURE 3
FIGURE 3
Overview of the diversity of the immune cell landscape during kidney allograft rejection. Different immune cells from innate (orange boxes) and adaptive (purple boxes) immunity are involved during the course of kidney transplant rejection. There are classified as minor components, major components and tertiary lymphoid organs (TLO). These components may play a role into acute and chronic rejection, whether in T-cell mediated rejection or antibody-mediated rejection.
See this image and copyright information in PMC

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