Theophylline-resistant and theophylline-sensitive "active" and "total" E rosette-forming lymphocytes in patients with...

Using the E rosette test and its modification with theophylline, we have studied T regulatory lymphocytes in various forms of systemic scleroderma. Mean percentages of active rosette-forming cells (ARFC) as well as the fraction resistant to theophylline incubation (ARFC-res) were significantly decreased, irrespective of the variety of the disease, compared to the age-matched controls. Late ("cold") rosette-forming fractions were unimpaired. The theophylline-sensitive fraction of total rosette-forming cells (TRFC-sens), which contains mainly cells from the suppressor circuit, was found to be lowered in all patients groups studied, whereas the ARFC-sens fraction was significantly decreased only in patients with diffuse scleroderma over 50 years of age, in whom there was a tendency to a more severe course, as manifested by pronounced systemic organ involvement. The lowered values of E rosette tests were found in a majority of SSc patients and were correlated with the appearance in the sera of factors capable of inhibiting ARFC formation by normal human peripheral blood T lymphocytes. Normal values of the E rosette test were related to the presence in the patients' sera of factors stimulating ARFC formation by normal lymphocytes. We surmise from the results that in SSc patients the T-cell defect is not only restricted to T suppressor cells but also refers to the active theophylline-resistant fraction containing mainly T inducer and T cytotoxic cells.