Background/Purpose: To investigate the effect of low-dose IL-2 on the balance of Treg with Teff and other pro-inflammatory lymphocytes in peripheral blood of pSS patients.

Methods: A total of 190 pSS patients and 30 healthy controls were included in the study. The absolute numbers of total CD4+ T, CD8+ T, B, and NK cells in peripheral blood were determined using flow cytometry and BD Trucount^TM tubes, while the percentage of each cell subpopulation and CD4+ cell subsets was measured, and then calculated their absolute numbers. Of the 190 patients, 88 were given subcutaneous injections of small doses of recombinant human IL-2 (rhIL-2, 50*10⁶ IU/day for 5 days) in combination with standard therapy, including glucocorticoids, immunosuppressants, Treatment of biologics or their combinations, while other patients received only standard therapies.

Results: (1) The absolute number of peripheral Treg cells of pSS patients was significantly lower than that of normal controls. (2) The absolute number of Th17 and CD8+ T cells before treatment was not different from that of normal controls, whereas the ratios of Th17/Treg and CD8+T/Treg were higher than normal, indicating that the imbalance of them was caused by insufficient number of Treg cells. Although Th17 and CD8+ T cells increased, Treg cells increased more dramatically, so the ratio returned to normal. Similarly, Th1, Th2, NK, and B cells had similar changes, as shown in Figure 2. (3) Compared with the standard treatment group, low-dose IL-2 increased the proportion of the patients with balanced Th17/Treg, who had a more pronounced improvement in symptoms, and less usage of glucocorticoid and HCQ. (4) There were positive correlations between ESSDAI value and the ratios of Th17/Treg (r=0.121, P=0.01), Th1/Treg (ρ=0.103, P<0.05), Th2/Treg (ρ=0.123, P<0.01), B/Treg (ρ=0.122, P<0.05), CD8+T/Treg (ρ=0.107, P<0.05), but no correlation between ESSDAI value and the ratio of NK/Treg (ρ=0.011, P>0.05).

Conclusion: Low-dose rhIL-2 treatment can promote the proliferation of various cell subsets, but mainly Treg cells, indicating that this treatment can restore the overall balances of Teff/Treg, B/Treg, and NK/Treg. Thus, due to improvement of ESSDAI, the overall balances between Treg and pro-inflammation cells are more important than the change in the single cell subset.