Alteration of CD4(+)CD25(+)Foxp3(+) T cell level in Kawasaki disease

PURPOSE: Exaggerated pro-inflammatory reactions during the acute phase of Kawasaki disease (KD) suggest the role of immune dysregulation in the pathogenesis of KD. We investigated the profiles of T regulatory cells and their correlation with the clinical course of KD. METHODS: Peripheral blood mononuclear cells were collected from 17 KD patients during acute febrile and subacute afebrile phases. T cells expressing CD4, CD25, and Foxp3 were analyzed using flow cytometry, and the results were correlated with the clinical course of KD. RESULTS: The percentage of circulating CD4(+)CD25(high)Foxp3(+) T cells among CD4(+) T cells was significantly higher during the subacute afebrile phase than during the acute febrile phase (1.10%±1.22% vs. 0.55%±0.53%, P=0.049). Although levels of CD4(+)CD25(low)Foxp3(+) T cells and CD4(+)CD25(-)Foxp3(+) T cells were only slightly altered, the percentage of CD4(+)CD25(+)Foxp3(-) T cells among CD4(+) T cells was significantly lower during the subacute afebrile phase than during the acute febrile phase (2.96%±1.95% vs. 5.64%±5.69%, P=0.036). Consequently, the ratio of CD25(high)Foxp3(+) T cells to CD25(+)Foxp3(-) T cells was higher during the subacute afebrile phase than during the acute febrile phase (0.45%±0.57% vs. 0.13%±0.13%, P=0.038). CONCLUSION: Decreased CD4(+)CD25(high)Foxp3(+) T cells and/or an imbalanced ratio of CD4(+)CD25(high)Foxp3(+) T cells to CD4(+)CD25(+)Foxp3(-) T cells might play a role in KD development. Considering that all KD patients were treated with intravenous immunoglobulin (IVIG), recovery of CD4(+)CD25(high)Foxp3(+) T cells during the subacute afebrile phase could be a mechanism of IVIG.