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Increased frequency of interleukin 4 producing CD4+ and CD8+ cells in peripheral blood from patients with systemic
J Tsuji-Yamada1, M Nakazawa, M Minami
1Department of Dermatology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Objective:
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.
Methods:
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.
Results:
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.
Conclusion:
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.