Partial Character izat ion and Spec t rum of Activity Against Normal and Malignant

Several glycoproteins or polypeptides that are produced by T cells in culture (T lymphokines) and that inhibit cell proliferation in vitro have been identified and characterized. Two of these factors, immune interferon (IFN-3') (1-3) and one member of the lymphotoxin (LT) 1 family (4-6), have been purified to homogeneity, cloned, and sequenced (1-3, 7, 8). Several others are at different stages of characterization and, based on their most prominent biological activity, have been designated: inhibitor of DNA synthesis (IDS) (9-I I); suppressor cell induction factor (SIF) (12, 13); macrophage migration inhibitory factor (MIF) (4, 14); soluble immune suppressor supernatants (SISS-T and SISS-B) (15, 16), which inhibit T cell proliferation or B cell Ig production; B cell growth inhibitory factor (BIF) (17); suppressor activating factor (SAF) (18, 19); soluble immune response suppressor (SIRS) (20-23); a factor that inhibits mouse bone marrow and leukemia cell proliferation (STIF) (24); and colony-inhibiting lymphokine (CIL), a factor that inhibits colony formation of human bone marrow progenitor cells (25). Several of these factors (LT, BIF, SISS-B, CIL) have been shown by column chromatography to have M, of 70,000-90,000, and their possible unique identity has been attributed either to their specific physicochemical characteristics (heat and pH sensitivity) or to their spectrum of target reactivity. Part of the problem hampering the rapid purification and definitive characterization by protein and nucleic acid sequencing of these lymphokines lies in the fact that most are produced in small amounts by short term cultures of human PBL stimulated to proliferate by mitogens or alloantigens. Some factors, however, are abundantly elaborated by T cell lines: SAF is produced by a subclone of the 6-thioguanine (6TG)-resistant human leukemic T cell line CEM