Antiproliferative effect of IFN-gamma on proliferation of mouse connective tissue-type mast cells

Mouse rIFN-gamma suppressed clonal growth of tissue-type mast cells (CTMC) separated from mouse peritoneal cells (greater than or equal to 98% purity) in methylcellulose culture containing IL-3 + IL-4 in a dose-dependent fashion. The IFN-gamma-mediated suppression was also observed both in serum-free culture and in single-cell culture. In addition, mAb to mouse IFN-gamma neutralized the suppressive effect of IFN-gamma on CTMC proliferation supported by the combination of IL-3 + IL-4. These observations suggest a direct antiproliferative effect of IFN-gamma on CTMC. No suppression of CTMC proliferation was observed when CTMC were washed with alpha-medium after 24 h of preincubation with IL-3 + IFN-gamma and then cultured in methylcellulose medium containing IL-3 + IL-4. IFN-gamma had suppressive effects on CTMC after preincubation with IL-3 + IL-4. These preincubation studies suggest that IFN-gamma exerts a reversible inhibitory effect on CTMC which have entered into a proliferative state by IL-3 + IL-4, and has neither cytotoxic nor irreversible suppressive effects on resting CTMC in cultures containing IL-3 alone. CTMC proliferation after stimulation with the cross-linking of cell-bound IgE by specific Ag in the presence of IL-3 was also suppressed by IFN-gamma. By contrast, proliferation of CTMC induced by the combination of 12-O-tetradecanoyl phorbol-13-acetate + IL-3 was not affected by the addition of IFN-gamma to the culture. Based on these observations, we suggest that IFN-gamma antagonizes the colony inducing effect of IL-4 and IgE-Ag stimulation which act synergistically with IL-3 on CTMC.