IL-17+/IL-10+ Ratio in TCRαβ+ CD4- CD8- T Cells As a Marker of Disease Activity in Lupus-Prone Mice and Patients With Systemic Lupus Erythematosus.

OBJECTIVE

T cell receptor αβ+ (TCRαβ+) CD4- CD8- double-negative (DN) T cells are expanded in lupus-prone mice and patients with systemic lupus erythematosus (SLE), produce interleukin-17 (IL-17), and contribute to disease pathogenesis. However, it is not known whether there is functional heterogeneity within this population. This study aimed to determine whether a subset of DN T cells produces IL-10 and whether the ratio of IL-17+/IL-10+ DN T cells correlates with disease activity.

METHODS

Flow cytometry was used to analyze DN T cells in lupus-prone MRL/lpr mice and patients with SLE. IL-17+ and IL-10+ DN T cells were identified and quantified in the peripheral blood and lymphoid organs. Correlations between the IL-17+/IL-10+ DN T cell ratio and clinical parameters, including the SLE Disease Activity Index (SLEDAI) and proteinuria, were examined.

RESULTS

IL-17+ DN T cells were increased in lupus-prone mice, whereas IL-10+ DN T cells decreased in aging MRL/lpr mice. In patients with SLE (n = 67), the IL-17+/IL-10+ DN T cell ratio was associated with higher SLEDAI scores and was elevated in those with proteinuria. A longitudinal analysis of patients with SLE similarly showed a positive correlation between SLEDAI scores and the IL-17+/IL-10+ DN T cell ratio.

CONCLUSION

The observation of nonoverlapping IL-10+ and IL-17+ DN T cells suggests heterogeneity within the DN T cells in both lupus-prone mice and patients. The IL-17+/IL-10+ DN T cell ratio may serve as a biomarker to monitor disease activity in patients with SLE.