Abstract
OBJECTIVE: To determine serum cytokine concentrations and intracellular cytokine production of CD4+ and CD8+ T cells in 20 patients with mixed connective tissue disease (MCTD). METHODS: Detailed analysis of cytokine production; 8 patients were in the active stage, 12 in the inactive stage of the disease. Serum concentrations of interferon-gamma (IFN-gamma), interleukin 4 (IL-4), and IL-10 were assessed by ELISA. Intracellular content of IFN-gamma, IL-4, and IL-10 in CD4+ and CD8+ peripheral blood T cell and lymphocyte subsets was determined by flow cytometry. RESULTS: Serum concentrations of both type 1 and type 2 cytokines were significantly higher in patients with MCTD than in healthy controls. IFN-gamma expression of CD4+ and CD8+ T cells did not differ comparing all patients to controls. In patients with active MCTD, the percentage of CD8+/IFN-gamma+ Tc1 cells was significantly increased compared to inactive disease or to controls (p < 0.05). IL-4 expression of CD4+ T cells was scarcely detectable in MCTD, while a subpopulation of CD8+ Tc2 cells produced IL-4. A higher percentage of these CD8+/IL-4+ Tc2 cells were detected in patients with MCTD, especially in active disease, compared to controls (p < 0.05). The percentage of IL-10-expressing CD4+ and CD8+ T cells was higher in patients than in controls (p < 0.05). Again, CD4+ and CD8+ T cells from patients with active MCTD produced significantly more IL-10 than cells in patients with inactive disease or in controls (p < 0.05). CONCLUSION: Our results suggest that MCTD is associated with increased production of both type 1 (IFN-gamma) and type 2 cytokines (IL-4, IL-10). Cytokine production is usually higher in active MCTD than in inactive disease. CD8+ T cells may produce more IFN-gamma and IL-10 in comparison to CD4+ T cells. Patients with active disease have more IL-4-expressing Tc2 cells and IL-10-expressing Th2 and Tc2 cells than patients with inactive MCTD or controls. In MCTD, increased IL-10 production by Th2 and Tc2 cells may be an attempt by the immune system to downregulate the inflammatory reaction, although this effect may not be sufficient to restore the physiological Th1/Th2 balance in MCTD.
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