MACROPHAGES ARE DISPENSABLE FOR SUPERANTIGEN-MEDIATED STIMULATION ANDANERGY INDUCTION OF PERIPHERAL T-CELLS IN-VIVO

Bacterial superantigens provoke T lymphocyte activation by cross-linki ng the variable part of the T cell receptor (TCR) beta-chain with MHC class II molecules on antigen-presenting cells. Although the molecular mechanisms of this interaction are well characterized, the in vivo ac cessory cell requirements for this stimulation of T lymphocytes by bac terial superantigens remain unknown. In the present study we have addr essed the role of splenic macrophages in the activation of V beta 8(+) peripheral T cells by staphylococcal enterotoxin B (SEB) in BALB/c mi ce. SEP-triggered clonal expansion and subsequent induction of unrespo nsiveness of both CD4(+) and CD8(+) T cells were investigated in naive animals, or in mice injected intravenously with dichloromethylene dip hosphonate-containing liposomes. Such a treatment resulted in the comp lete and long-lasting elimination of the splenic macrophage population . Remarkably, however, this complete depletion of peripheral macrophag es had only a rather minor effect on the superantigen-induced T cell r esponse in the spleen, and macrophage-depleted animals exhibited overa ll the same magnitude and kinetics of SEB-mediated T cell activation a nd anergy-induction as their nondepleted counterparts. Our data thus e xclude an essential role of peripheral macrophages or macrophage-secre ted cytokines in the systemic T cell activation caused by bacterial su perantigens in vivo. (C) 1994 Academic Press, Inc.