Increased proportion of CD4 super(+) CD25 super(+) Foxp3 super(+) regulatory T cells during early-stage sepsis in ICU patients

Background/Purpose(s): We investigated whether CD4 super(-)CD25 super(-)Foxp3 super(-) regulatory T cells (Tregs) are induced in patients suffering from early-stage septic shock and distinguish them from noninfectious patients with systemic inflammatory response. Methods: The study included 37 patients with early-stage septic shock, 15 patients with noninfectious systemic inflammatory response syndrome (SIRS), and 24 heath controls. We prospectively assayed the fraction of Tregs expressing high levels of CD25 and forkhead box P3 (Foxp3) as well as the plasma levels of interferon- gamma (IFN- gamma ), interleukin-4 (IL-4), and soluble CD25 in all the subjects studied. Results: Compared with the control groups, the plasma levels of IFN- gamma [66.10 (45.23-85.08) pg/mL vs. 20.97 (17.58-26.21) pg/mL, p < 0.001] and IL-4 [100.69 (77.41-127.68) pg/mL vs. 70.40 (64.14-80.15) pg/mL, p < 0.001] as well as the IFN- gamma /IL-4 ratio [0.66 (0.62-0.67) vs. 0.30 (0.27-0.33), p < 0.001] were significantly elevated in the patients with early-stage septic shock, but there was no difference between patients with sepsis and patients with SIRS. We found that the proportion of CD4 super(-)CD25 super(-) Foxp3 super(-) T cells was significantly increased in the patients with early-stage septic shock [(66.82 plus or minus 21.79%) vs. (51.79 plus or minus 21.79%) vs. (56.45 plus or minus 10.68%), p = 0.003] in comparison with the SIRS and control groups, which could be differentiated from the patients with SIRS. The plasma levels of soluble CD25 were also increased, and positively correlated with the proportion of Tregs in patients with early-stage septic shock (Spearman correlation coefficient = 0.390, p = 0.003). Conclusion: Our findings indicate that the proportion of CD4 super(-)CD25 super(-) Foxp3 super(-) T cells could be an indicator for the early diagnosis of sepsis. This proportion can also facilitate the evaluation of the patient's immune status and guide suitable immunoregulatory therapy.