Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus

Abstract

Objective

Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE.

Methods

Circulating γδ-T cells and their subsets (Vδ1⁺ T cells, Vδ2⁺ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed.

Results

Compared with that in HCs, the percentage of total γδ-T cells among CD3⁺ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1⁺ and Vδ2⁺ T cells among γδ-T cells was observed. The proportion of Vδ1⁺ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2⁺ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1⁺ T cells and Vδ2⁺ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2⁺ T cells. Moreover, Vδ2⁺ T cells, Vδ1⁺ T cells and Vδ1⁺PD-1⁺ T cells were associated with disease activity, and an increase in Vδ2⁺ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2⁺ T cells and their Vδ2⁺NKp30⁺ T-cell subpopulation might be associated with renal involvement in SLE.

Conclusion

A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2⁺ T cells and their Vδ2⁺NKp30⁺ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.