Elsevier

The Journal of Pediatrics

Volume 145, Issue 3, September 2004, Pages 385-390
The Journal of Pediatrics

Original Articles
CD25+CD4+ regulatory T cells in patients with Kawasaki disease

https://doi.org/10.1016/j.jpeds.2004.05.048Get rights and content

Objective

To investigate whether the CD25+CD4+ regulatory T-cell population, which plays important roles not only in maintaining immunologic self-tolerance but also in controlling the magnitude and character of antimicrobial immune responses, is related to the pathophysiology of Kawasaki disease (KD).

Study design

The patient group consisted of 54 patients (median age, 30 months; 27 female and 27 male patients) fulfilling the criteria for KD. Age-matched control subjects included 17 patients with active infections and 24 healthy children. We analyzed CD25+CD4+ cells and the mRNA expression of Foxp3, cytotoxic T lymphocyte–associated antigen 4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and transforming growth factor β in peripheral blood mononuclear cells and purified CD4+ T cells.

Results

The proportions of CD25+CD4+ cells in patients with acute-phase KD (median, 2.35% of total lymphocytes) were significantly lower than those in healthy control subjects (median, 3.14%) and control subjects with disease (median, 3.15%). The proportions returned to the normal level after intravenous gammaglobulin treatment (median, 3.86%). The mRNA expression of Foxp3, CTLA4, and GITR showed similar tendencies.

Conclusions

The decrease of CD25+CD4+ regulatory T cells in the acute phase might have a role in the development of KD.

Section snippets

Patients

All patients enrolled in this study were admitted to the Kyushu University Hospital or its affiliated hospitals between December 2002 and May 2003. The patient group consisted of 54 patients (median age, 30 months; 27 female and 27 male patients) fulfilling the criteria for KD.30 No patients had coronary arterial lesions. CD4+CD25+ cells were analyzed in 54 patients before treatment with 1 g·kg−1·d−1 intravenous immunoglobulin (IVIG) and in the defervescence phase approximately 48 to 72 hours

CD25+CD4+ cells in KD

We first analyzed the proportions of CD25+CD4+ cells in the peripheral blood of 54 patients with KD by using flow cytometry. As shown in Figure 1, a, the proportions of CD25+CD4+ cells at the acute phase of KD (median, 2.35%; 10th percentile, 1.25%; and 90th percentile, 3.48% of total lymphocytes) were significantly lower than those in healthy control subjects (median, 3.15%; 10th percentile, 2.21%; and 90th percentile, 4.34%). At the defervescence phase of KD, these cell proportions

Discussion

Regulatory T cells are naturally occurring lymphocytes that have been shown to play central roles in immune regulation. Baecher-Allan et al33 demonstrated that the regulatory CD4+ T cells in peripheral blood of healthy human subjects preferentially reside within the CD25high CD4+ T-cell population. Although specific molecular markers for regulatory T cells in human subjects have not yet been fully established, it is suggested that Foxp3, CTLA4, and GITR are associated with regulatory T cells.27.

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