To study the mechanisms that regulate the activity of interleukin 2 (IL 2) and possibly limit its activity, we have examined normal human serum for its ability to inhibit IL 2-mediated proliferation of a cloned IL 2-dependent cytotoxic T lymphocyte line (CTLL). Normal human serum contains a factor capable of inhibiting IL 2 dependent proliferation of CTLL cells. This factor is absorbed with the cells but not IL 2 molecules. The inhibitor is heat-labile and inactivated by trypsin treatment. The molecular weight of the inhibitor is 70,000––220,000. The imbalance of the inhibitor is observed in serum from patients with autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis. These results suggest that the serum IL 2 inhibitor may play an important role in the in vivo regulatory mechanism of IL 2 activity and in aberrant immune functions in hum
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