Increased frequency of interleukin 4 producing CD4+ and CD8+ cells in peripheral blood from patients with systemic sclerosis.

Abstract

To-determine the relationship between the frequency of cytokine producing cells and systemic sclerosis (SSc), we examined the frequencies of interleukin 4 (IL-4) or IL-2 producing CD4+ or CD8+ T cells in peripheral blood mononuclear cells (PBMC) from patients with SSc. PBMC from 23 SSc patients and 14 healthy controls were isolated from heparinized blood by density centrifugation. Purified PBMC were stimulated with immobilized anti-CD3 monoclonal antibody for 6 h in the presence of monensin. Cells were fixed, made permeable, and stained for intracellular cytokines in combination with staining for T cell surface markers, CD4, and CD8. The frequency of CD4+ T cells was negatively correlated with duration of SSc, whereas the frequency of CD8+ T cells was not correlated with duration. The frequencies of IL-4 producing (IL-4+) cells in CD4+ T cells and in CD8+ T cells from patients with SSc were both significantly higher than those from controls. In contrast, the frequencies of IL-2 producing (IL-2+) cells in CD4+ T cells and in CD8+ T cells from patients with SSc were both significantly lower than that from controls. Further, the ratios of IL-4+/IL-4+ + IL-2+ in CD4+ T cells and in CD8+ T cells were both negatively correlated with disease duration of SSc. These results suggest that type 2 cytokine producing T cells, not only CD4+ T cells but also CD8+ T cells, have important roles in the pathogenesis of SSc, especially in the early phase of SSc.