Increased KIR + CD8+ T cell frequency with impaired cytotoxic potential in systemic lupus erythematosus.

OBJECTIVES

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that causes severe immune dysfunctions. Recent insights have identified CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) as potentially playing a significant role in immune regulation in autoimmune diseases. This study aimed to investigate the role of KIR+CD8+ regulatory T cells in SLE.

METHODS

A cross-sectional analysis encompassed 53 individuals with SLE and 42 healthy controls (HC). Analyze lymphocyte subsets and activation effector phenotypes by flow cytometry; assess cytokine secretion and cytotoxic functions of KIR+CD8 + T cells, as well as perform differential gene expression analysis.

RESULTS

SLE patients exhibit distinct immunological characteristics, with a significant reduction in lymphocyte absolute counts, alongside a marked increase in the proportions of effector CD4 + T cells, plasmablast, and CD8 + CD28-T cells, yet the levels of regulatory T cells (Treg cells) show no difference compared to those in HC. CD8 + T cells highly express KIRs in SLE, and there is a negative correlation between the levels of CD158e + CD8 + T cells and disease activity. Furthermore, in SLE patients, KIR+CD8 + T cells exhibit elevated PD-1 expression, coupled with a diminished capacity for cytokine secretion, notably gamma-interferon (IFN-γ). These cells demonstrate impaired cytotoxic potential, with downregulation of cytotoxicity-related genes and reduced expression of cytotoxic protein such as perforin.

CONCLUSION

KIR+CD8+ T cells, as an essential component of immune regulation, are significantly elevated in SLE, but their perforin expression is reduced, suggesting that its cytotoxic potential may be impaired, leading to impaired immune regulatory functions.