Con A-induced suppressor cells in man II. Role of monocytes and their interaction with soluble inhibitory factors

Abstract

Monocyte dependence of Con A-induced suppression was studied in co-cultures of normal human lymphocytes. Con-A-pretreated (25 µg/ml for 48 hours) peripheral blood mononuclear (MN) cells inhibited the 3H-thymidine uptake by fresh autologous or allogeneic lymphocytes stimulated with Con A. Monocyte-depleted lymphocytes pretreated with 25 µ/ml of Con A failed to exhibit the suppressor properties. Supernatants of MN cell activated with 25 µ/ml Con A for 72 hours inhibited the mitogenic response of fresh allogeneic cells when added in proportion 1 : 1 to the culture medium. No inhibition was observed when supernatants of monocyte-depleted, Con A activated cultures were tested. The short preincubation with suppressive supernatants rendered blood adherent mononuclear cells suppressive for 3H-thymidine incorporation by autologous MN cells stimulated with Con A. These studies indicate that monocytes are essential for induction of suppressor cells in Con A stimulated cultures. The suppressor cells produce a soluble inhibitory factor(s) which has the property of binding to the surface of fresh monocytes. Such monocytes become responsible for suppression of mitogenic response of autologous lymphocytes.