Circulating CD8 + LGALS9 + T Cell Population Exhibiting Low Cytotoxic Characteristics are Decreased in Patients with Systemic Lupus Erythematosus

Immunol Res. 2024 Dec;72(6):1238-1246. doi: 10.1007/s12026-024-09522-4. Epub 2024 Jul 24.

Abstract

LGALS9, also known as Galectin-9 and a member of the β-galactosidase family, plays a crucial role in immune regulation. However, its expression and function in CD8 T cells, as well as its association with cytotoxic T lymphocytes (CTL), remain unclear. This study aims to investigate LGALS9 expression patterns in human circulating CD8 T lymphocytes and elucidate its clinical significance in Systemic Lupus Erythematosus (SLE). Blood samples from 56 healthy controls and 50 new-onset SLE patients were collected. Flow cytometry was utilized to analyze LGALS9 expression in circulating CD8 T lymphocytes via intracellular staining. Compared to LGALS9 + CD8 + T cells, LGALS9-CD8 + T cells showed increased secretion of Granzyme B (GZMB) and Perforin, along with elevated expression levels of GPR56, CX3CR1, KLRD1, KLRF1, PD1, and CD29. A higher proportion of Tn (naive T cells) and TCM (central memory T cells) showed LGALS9 positivity, compared to TEM (effector memory T cells) and TEMRA (terminally differentiated effector memory T cells re-expressing CD45RA). Clinically, the downregulation of LGALS9 expression was significant in SLE patients. LGALS9 + CD8 + T cells exhibited an Area Under the Curve (AUC) of 0.6916, while CX3CR1 + in LGALS9 + CD8 + T cells had an AUC of 0.6478, and KLRF1 + had an AUC of 0.6419, for distinguishing SLE from healthy individuals. In conclusion, CD8 + LGALS9 + T cells display characteristics of low cytotoxicity, and their reduction is evident in SLE patients, potentially implicating them in SLE pathogenesis and providing diagnostic assistance.

Keywords: CD8 CTLs; Galectin-9; SLE; diagnosis.

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes* / immunology
  • Cytotoxicity, Immunologic*
  • Female
  • Galectins* / metabolism
  • Granzymes / metabolism
  • Humans
  • Lupus Erythematosus, Systemic* / immunology
  • Male
  • Middle Aged
  • Perforin / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Young Adult

Substances

  • LGALS9 protein, human
  • Galectins
  • Perforin
  • Granzymes