T-derived colony-inhibiting activity: partial characterization and mechanism of action

A soluble inhibitor of granulocyte macrophage colony growth, to which we shall refer to as T-derived colony-inhibiting activity (Td/CIA), was obtained from the supernatant of T cells from 5 healthy donors and 5 patients with severe aplastic anemia (SAA) in remission, following immunosuppressive therapy. The supernatants were purified by an ACA 44 column and the suppressor activity found in fractions of 70,000-80,000 daltons. Experiments were then performed to test for endogenous productions of Td/CIA in normal marrow cells (NBM), reversibility of suppression, and competitive inhibition with human placenta-conditioned medium (HPCM). The results of this study can be summarized as follows: the endogenous production of Td/CIA can be elicited by addition of mitogens to NBM, and is prevented if the marrow is T-depleted or treated with cyclosporin A; suppression is completely reversible if Td/CIA is removed from NBM by washing at 1, 48, 72 and 96 h; CFU-c which have been exposed to Td/CIA once, and freed from Td/CIA by washing, are still sensitive to a second exposure of Td/CIA; there is no clear competitive inhibition between Td/CIA and HPCM. These experiments represent an in vitro model of a lymphokine-mediated regulation of CFU-c growth not associated with death of progenitor cells.