Response of T-cell Subpopulations to Superantigen and Recall Antigen Stimulation in Systemic Sclerosis

BACKGROUND: There is great disagreement regarding which effector T-cells are responsible for the pathogenesis of systemic sclerosis. Further, the possible role of superantigens in modulating the T-cell phenotype responsible for the immunopathogenesis of this disease and the response of these patients to common recall antigens have not been adequately determined. AIMS: To investigate the T-cell subsets and activation markers in peripheral blood mononuclear cells of systemic sclerosis patients before and after stimulation with different bacterial superantigens and common recall antigens to better understand the immunopathogenesis of this disease. MATERIALS AND METHODS: T-cells (CD3(+)) from 20 systemic sclerosis patients and 17 age-matched healthy controls were studied using flow cytometry for the expression of CD4, CD8, CD45RA, and CD45RO at baseline and upon stimulation with different superantigens and recall antigens. Patients were also tested for skin delayed hypersensitivity to common recall antigens. RESULTS: The proportions of CD45RA(+) (naive) and CD45RO(+) (memory) CD4(+) T-cells were found to be significantly higher in patients than in controls upon stimulation with bacterial superantigens. However, T-cells from these patients responded weakly to recall antigen stimulation, indicating a loss of specific memory cells. This was further supported by the skin delayed hypersensitivity test in which 16 patients were found to be anergic. CONCLUSIONS: Our findings suggest that both naïve (CD45RA(+)) and memory (CD45RO(+)) CD4(+) superantigen-reactive T-cells are effector T-cells that may modulate the pathogenic autoantibody response in systemic sclerosis. Accumulation of these cells in these patients may result in increased risk of relapses and resistance to therapy.