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

Objective: Human gamma-delta T cells (gamma delta-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of gamma delta T cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of gamma delta-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. Methods: Circulating gamma delta-T cells and their subsets (V delta 1(+) T cells, V delta 2(+) T cells and gamma delta-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 gamma delta-T cells among CD3(+) T cells in SLE patients was significantly lower. An imbalance in the proportions of V delta 1(+) and V delta 2(+) T cells among gamma delta-T cells was observed. The proportion of V delta 1(+) T cells among gamma delta-T cells was significantly greater in SLE patients than in HCs, while the proportion of V delta 2(+) T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in V delta 1(+) T cells and V delta 2(+) T cells from SLE patients were generally significantly increased, except for expression of NKG2D in V delta 2(+) T cells. Moreover, V delta 2(+) T cells, V delta 1(+) T cells and V delta 1(+)PD-1(+) T cells were associated with disease activity, and an increase in V delta 2(+) T-cell frequency and a decrease in PD-1 expression by gamma delta-T cells might be associated with effective treatment. Interestingly, our results indicated that V delta 2(+) T cells and their V delta 2(+)NKp30(+) T-cell subpopulation might be associated with renal involvement in SLE. Conclusion: A broad range of anomalies in the proportions of gamma delta-T-cell subsets and gamma delta-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between V delta 2(+) T cells and their V delta 2(+)NKp30(+) T-cell subpopulation and LN occurrence. Our results indicate that gamma delta-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.