Dual inhibitory and stimulatory activities in serum from SLE patients and lupus mice that regulate the proliferation of an IL-2-dependent T cell line

Abstract

In serum and plasma from SLE patients, we have detected elevated levels of factors which regulate proliferative responses of CTLL cells to IL-2. Serum samples containing these factors have dose-dependent dual inhibitory and stimulatory activities on the proliferation of this IL-2-dependent T lymphocyte cell line. At high concentrations, the serum factors inhibit the proliferative responses of CTLL cells to IL-2. At low concentrations, they synergise with IL-2 stimulating the growth of cells. Similar inhibitory activity, but with lower titre, was also found to be elevated in sera of some MRL/ lpr mice, an animal model of SLE. Functional characterisation of the serum factors shows that: (1) the inhibitory activity cannot be neutralised by exogenous IL-2; (2) the stimulatory activity is not due to the presence of serum IL-2 but synergy of the factor with IL-2; (3) the factors bind directly to CTLL cells but they do not bind to protein A; and (4) the serum factors are not dialysable but heat labile. The possible pathological implications of the serum factors, particularly for the defective T cell functions in lupus disease, are discussed.