Table 1.
Clinical characteristics of the enrolled sarcoidosis patients (n = 42).
Fig 1.
The distributions of Th1, Th2, Th17 and Treg cells in the peripheral blood in relapsed and stable pulmonary sarcoidosis patients after corticosteroid withdrawal.
IFN-γ+CD4+ T cells were defined as Th1 cells, IL-4+CD4+ T cells were defined as Th2 cells, IL-17A+CD4+ T cells were defined as Th17 cells, and Foxp3+CD25+CD4+ T cells were defined as Treg cells. (A) Gating strategy for analysis of IL-17A-, IFN-γ-, and IL-4-expressing CD4+ T cells sorted from lymphocytes by ICCS. The values in the quadrants indicate the percentages of each CD4+ T cell subset. (B) Representative dot plots of Th17 and Th1 cells in the peripheral blood of relapsed and stable patients. (C) Gating strategy for analysis of Foxp3+CD25+ cells in the CD4+ T population sorted from lymphocytes by ICCS. CD25+Foxp3+ cells were gated to correspond to the isotype control. (D) Pooled data demonstrating the percentages of gated Th1, Th2, Th17 and Treg cells from CD4+ T cells in relapsed and stable pulmonary sarcoidosis patients after corticosteroid withdrawal. The percentage of Treg cells and the Treg/Th17 ratio in the stable patients were higher than those in the relapse patients, while the percentage of Th17 cells was lower in the stable patients (p<0.05). There were no differences in the percentage of Th1 cells or Th2 cells between the two groups.
Table 2.
Clinical characteristics of remission patients who underwent retreatment (n = 16).
Fig 2.
The percentages of Th1, Th2, Th17, and Treg cells at the onset of relapse and at remission after 12 weeks of retreatment.
The percentage of Treg cells and the Treg/Th17 ratio were increased after retreatment in the relapsed sarcoidosis patients; this increase was accompanied by a decrease in the percentage of Th17 T cells (p<0.05). The percentages of Th1 and Th2 cells did not differ between the relapsed and remission patients.
Fig 3.
The Treg/Th17 ratio was correlated with serum ACE and FEV1% and DLco% predicted values in relapsed sarcoidosis patients. Each dot represents a value measured before or after retreatment.
(A) The Treg/Th17 ratio and serum ACE showed a negative correlation in the relapsed patients.(B) The Treg/Th17 ratio demonstrated a moderate positive correlation with the FEV1% predicted value in the relapsed patients.(C) The Treg/Th17 ratio demonstrated a moderate positive correlation with the DLco% predicted value in the relapsed patients.
Fig 4.
Proliferative activity of Tregs isolated by MACS via in vitro culturing.
(A) Representative dot plots of Ki-67+ Treg cells from the relapsed and stable patients. The stable patients showed a higher percentage of Ki-67+ Tregs compared with the relapsed patients. (B) Proliferative activity of Tregs in six relapsed patients. Activity at the onset of relapse was compared with activity after retreatment. The percentage of Ki-67+ Tregs was increased after retreatment, and that of CD45RO+Ki-67+ Tregs was increased after remission.
Fig 5.
Dynamic follow-up of the Treg/Th17 ratio, serum ACE and FEV1% and DLco% predicted values in pulmonary sarcoidosis patients.
(A) The Treg/Th17 ratio decreased, accompanied by an elevation in the serum ACE level and decreases in the FEV1% and DLco% predicted values over the nine months of follow-up after the end of treatment in the first relapse patient; then, the Treg/Th17 ratio dramatically increased, accompanied by a decrease in the serum ACE level and increases in FEV1% and DLco% predicted values over the first 3 months of retreatment. Over the 12 months of follow-up, these values stabilized. (B) The Treg/Th17 ratio decreased over 6 months of follow-up after the end of treatment, without distinct changes in the serum ACE or FEV1% and DLco% predicted values in another relapse patient; then, the Treg/Th17 ratio slightly increased over the first 3 months of retreatment, with symptom remission at 12 months of follow-up. (C) The Treg/Th17 ratio, serum ACE and FEV1% and DLco% predicted values remained stable before the end of prednisone treatment in a stable patient; all of these parameters remained stable without clinical symptoms over the subsequent 12 months.