Study of the association between CD28/CTLA-4 expression and disease activity in juvenile idiopathic arthritis

The aim of the present study was to investigate the immune function of children with juvenile idiopathic arthritis (JIA). Flow cytometry and three-color direct immunofluorescence were used to examine cluster of differentiation (CD)3⁺ T-lymphocyte subsets and CD28/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in whole blood (using the no-wash method) from 36 children with JIA and 39 healthy children. During the active phase of JIA, CD28 expression on CD4⁺ T cells in children with JIA was significantly reduced; thus, CD4⁺CD28^- T-cell frequency increased, suggesting that CD4⁺ T-cell and CD4⁺CD28^- T-cell apoptosis was inhibited in patients with JIA. The continued survival of these immune-active T lymphocytes may promote the occurrence and development of JIA. CTLA-4 expression levels on CD4⁺ and CD8⁺ T cells in children with JIA during the active phase were significantly higher than those in normal controls. As the majority of CD4⁺ T cells in patients with JIA are CD28^-, they cannot be inactivated by the interaction between CTLA-4 and B7, leading to continuously high levels of CTLA-4 expression on the surface of CD4⁺ T cells without functional effect. Hence, T lymphocytes are continuously kept in a highly activated state that is difficult to stop. During the resting phase, the CD4⁺ and CD8⁺ T-cell counts in children with JIA were similar to normal, and CD28 expression was also normal. This suggests that the frequency of CD4⁺CD28^- T cells can be used as an indicator of the active phase of JIA. CTLA-4 expression on the surface of T cells in children with JIA during the resting phase was also similar to that in normal controls, suggesting that abnormal lymphocyte activation plays an important role in the active phase of JIA.