CD107a+ (LAMP-1) Cytotoxic CD8+ T-Cells in Lupus Nephritis Patients.

Anika Wiechmann,Wayel H Abdulahad,Karl Sebastian Lang,Oliver Witzke,Bartosz Tyczynski,Sebastian Dolff,Andreas Kribben,Benjamin Wilde,Kerstin Amann

doi:10.3389/fmed.2021.556776

Abstract

Cytotoxic CD8+ T-cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate the role of CD107a (LAMP-1) on cytotoxic CD8+ T-cells in SLE-patients in particular with lupus nephritis. Peripheral blood of SLE-patients (n = 31) and healthy controls (n = 21) was analyzed for the expression of CD314 and CD107a by flow cytometry. Kidney biopsies of lupus nephritis patients were investigated for the presence of CD8+ and C107a+ cells by immunohistochemistry and immunofluorescence staining. The percentages of CD107a+ on CD8+ T-cells were significantly decreased in SLE-patients as compared to healthy controls (40.2 ± 18.5% vs. 47.9 ± 15.0%, p = 0.02). This was even more significant in SLE-patients with inactive disease. There was a significant correlation between the percentages of CD107a+CD8+ T-cells and SLEDAI. The evaluation of lupus nephritis biopsies showed a significant number of CD107a+CD8+ T-cells mainly located in the peritubular infiltrates. The intrarenal expression of CD107a+ was significantly correlated with proteinuria. These results demonstrate that CD8+ T-cells of patients with systemic lupus erythematosus have an altered expression of CD107a which seems to be associated with disease activity. The proof of intrarenal CD107a+CD8+ suggests a role in the pathogenesis of lupus nephritis.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various organ manifestations
Ligation of CD107a (LAMP-1) has been described as a pivotal axis which leads to CD8+ T-cell activation
The decreased proportion of CD107a+CD8+ T-cells was especially found in SLE-patients without lupus nephritis

Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by various organ manifestations. Inflammation of the kidney, in particular, is associated with an unfavorable prognosis (1). The precise pathogenesis of lupus nephritis (LN) has not been elucidated, disturbances in regulatory and effector T-cell balance seem to contribute to the development of LN (2). Despite an increasing body of evidence reporting CD4+ T-cell abnormalities, the role of cytotoxic CD8+ T-cells is less well-understood. CD8+ T-cells can contribute to autoimmunity by chemokine secretion which is capable to attract other immune cells, recruitment of autoreactive CD8+ T-cells and killing of target cells. In SLE an increase of activated CD8+ T-cells expressing perforin and granzyme B has been reported (3). The authors found intrarenal CD8+ T-cells in lupus nephritis biopsies.

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