CCR4⁺ memory Tregs and PD-1⁺ T cells as novel immunodiagnostic biomarkers for active tuberculosis.

Abstract

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis(M.tb), remains a major global infectious disease. T cell-mediated immune responses play a crucial role in host defense against TB. Investigating the differentiation and functional status of T cell subsets may help identify novel biomarkers for the diagnosis and prediction of active tuberculosis (ATB).

Methods: This study enrolled 140 ATB patients and 140 healthy controls (HC) to investigate the immunophenotypic differences in T cell subsets within peripheral blood mononuclear cells (PBMC). Univariate and multivariate analyses were conducted to evaluate the association between T cell subsets and TB infection, as well as their potential value in predicting ATB. Propensity score matching was used to analyze the immunophenotypic differences in PBMC between mild and severe ATB patients.

Results: Compared with HC, ATB patients exhibited higher frequencies of CD3⁺ T cells (P < 0.0001), lower frequencies of CD4⁺ central memory T cells (CM) (P < 0.01) and CD8⁺ Effector T cells (P < 0.05), and increased frequencies of CD8⁺ CM (P < 0.01). Expression of programmed cell death protein 1 (PD-1) on CD4⁺ and CD8⁺ T cells was downregulated, while Human Leukocyte Antigen - DR (HLA-DR) expression was upregulated. CCR4⁺ memory regulatory T cells (Tregs), CD8⁺PD-1⁺ T cells, and CD4⁺PD-1⁺ T cells were closely associated with TB infection and showed potential value in predicting ATB. Severe ATB patients had more CD8⁺ HLA-DR⁺ T cells (P < 0.05) and fewer CD4⁺ Effector T cells (P < 0.05).

Conclusion: Differentiation and function of T cell subset are associated with TB infection. CCR4⁺ memory Tregs, CD4⁺PD-1⁺ T cells, and CD8⁺PD-1⁺ T cells show potential predictive value for ATB.