CTLA-4 (CD152) Expression in T Cells during the Acute Stage of Kawasaki Disease

Although we have already reported that the activation of monocytes/macrophages plays a central role in acute Kawasaki disease (KD), the role of T cells in KD remains under debate. The kinetics of T cell activation in acute KD was investigated with emphasis on cytotoxic T lymphocytes-associated antigen 4 (CTLA-4, CD152). CTLA-4 is a surface molecule of activated T cells with sequence homology to CD28. Both molecules bind to the same ligands, but have antagonistic functions. While CD28 is an important costimulator, CTLA-4 has an essential inhibitory function in maintaining the homeostasis of the immune system. CTLA-4 is a negative regulator of T cell activation. Using flow cytometry, we investigated intracellular expression of CTLA-4 in CD3+ and CD4+T cells of 13 patients with KD and 13 healthy children. The percentages of intracellular CTLA-4 positive CD3+ and CD4+T cells were 6.6±3.7% and 4±3.8% in KD before treatment during the acute stage (Mean Illness Day: 3.9). These levels were significantly higher than the levels during the convalescent stage (1.8±1.4%, p<0.01 and 1.0±0.9%, p<0.05) and were significantly higher than the levels in healthy children (2.4±1.0%, p<0.01 and 1.0±0.6%, p<0.05). The percentages of CTLA-4+CD3+T cells and CD4+T cells were reduced after intravenous gammaglobulin treatment (3.9±4.2% and 3.3±4.2%, respectively). In this study, we found increases in CTLA-4 expression in T cells during acute KD. Since CTLA-4 is an inhibitory molecule of T cell activation, peripheral blood T cell activation seemed to have terminated by the time KD patients were diagnosed. Peripheral blood T cells might activate before symptoms appear in KD patients.