Functional inactivation of suppressor T cells by heat-killed macrophages

Abstract

WE have Shown that peritoneal exudate macrophages, killed by heating at 56 °C for 30min, can markedly suppress the antibody response to heterologous erythrocytes in primary Mishell–Dutton cultures¹. This heat treatment does not destroy the ability of the macrophages to form rosettes with sheep red blood cells (SRBCs) in the presence of cytophilic antibody, suggesting that some membrane surfaces remain undamaged. The heat treatment, however, does prevent the macrophages from excluding Trypan blue dye, indicating that the cells are no longer viable. Treatment of the macrophages at higher temperatures or with 0.1% glutaraldehyde destroys both their ability to form rosettes and to suppress Mislhell–Dutton cultures. Macrophage membranes, semppurified by separation on sucrose gradients, can act similarly—that is, suppress primary Mishell–Dutton cultures and form rosettes with SRBCs in the presence of cytophilic antibody (W.P. and R.K.G., unpublished). The heat-killed macrophages do not diminish the viability of the cell cultures even when they are maximally suppressive. We have interpreted these results to indicate that the dead macrophages suppress the immune response in culture by absorbing out, and thus rendering inoperative, some factors which are necessary for the cell interactions which result in the generation of plaque-forming cells. This contention is supported by the ability of the heat-killed macrophages to absorb out the helper activity found in the supernatants of mixed lymphocyte reactions (W.P. and R.K.G., unpublished). We reasoned that, if macrophages could absorb interaction factors, they might be able to absorb suppressive factors if they were added to a culture in which suppression was occurring and thus augment the response of suppressed but not normal cultures.