Alterations in Th17/Treg Balance and IL-21 Signaling in Patients with HIV and Mycobacterium tuberculosis Coinfection
Gao Chen, Shikai ChenIntroduction/Objective:
This study aimed to characterize the distributions of Th17 and regulatory T (Treg) cells and the associated interleukin-21 (IL-21) signaling in patients with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb) coinfection.
Methods:
This cross-sectional study included 54 participants in each of three groups: HIV/Mtb coinfection, Mtb monoinfection, and healthy control. Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient centrifugation. The percentages of Th17 and Treg cells, the Th17/Treg ratio, and the mean fluorescence intensity of IL-21 receptor (IL-21R) expression on Th17 cells were quantified by flow cytometry. Serum IL-21 concentrations were measured by enzyme-linked immunosorbent assay. Group comparisons were performed using non-parametric Kruskal-Wallis and Mann-Whitney U tests as appropriate.
Results:
The Th17/Treg cell ratio was significantly lower in both patient groups compared to the healthy control group (HIV/Mtb coinfection: 1.40 ± 0.35; Mtb monoinfection: 1.34 ± 0.28; healthy control: 2.50 ± 0.60; both p<0.001). Within the patient cohorts, the ratio was marginally but significantly higher in the HIV/Mtb coinfection group (p=0.047), primarily due to a higher proportion of Th17 cells (9.8±2.1% vs. 8.0±1.8%; p=0.021). Treg cell proportions did not differ significantly among the three groups (p=0.325). IL-21R expression on Th17 cells was higher in the HIV/Mtb coinfection group than in the Mtb monoinfection group (35.2±5.1% vs. 28.5±4.3%; p=0.035), while serum IL-21 levels were lower (105.0±20.0 pg/mL vs. 120.5±25.0 pg/mL; p=0.032). All patient values were lower than those in healthy controls (both p<0.001).
Discussion:
The concurrent findings—partial elevation of Th17/Treg ratio, compensatory upregulation of IL‑21R on Th17 cells, and profound systemic IL‑21 deficiency—suggest a dysregulated immune nexus in HIV/Mtb coinfection. This profile may reflect an attempt to mount Th17‑mediated responses against Mtb within a globally compromised immune system, potentially leading to ineffective pathogen control and heightened immunopathology. The IL‑21 axis appears critically impaired, with target cells possibly hypersensitized to scarce ligand via receptor upregulation.
Conclusion:
HIV/Mtb coinfection is associated with a distinct immunoprofile featuring a partially restored but still imbalanced Th17/Treg ratio, compensatory upregulation of IL-21R on Th17 cells, and systemic IL-21 deficiency. This dysregulated Th17/Treg-IL-21 axis may underlie the unique immunopathology of coinfection and warrants further investigation as a source of biomarkers or therapeutic targets.