Macrophages Are Dispensable for Superantigen-Mediated Stimulation and Anergy Induction of Peripheral T Cells in Vivo

Bacterial superantigens provoke T lymphocyte activation by cross-linking the variable part of the T cell receptor (TCR) β-chain with MHC class II molecules on antigen-presenting cells. Although the molecular mechanisms of this interaction are well characterized, the in vivo accessory cell requirements for this stimulation of T lymphocytes by bacterial superantigens remain unknown. In the present study we have addressed the role of splenic macrophages in the activation of Vβ8+ peripheral T cells by staphylococcal enterotoxin B (SEB) in BALB/c mice. SEB-triggered clonal expansion and subsequent induction of unresponsiveness of both CD4+ and CD8+ T cells were investigated in naive animals, or in mice injected intravenously with dichloromethylene diphosphonate-containing liposomes. Such a treatment resulted in the complete and long-lasting elimination of the splenic macrophage population. Remarkably, however, this complete depletion of peripheral macrophages had only a rather minor effect on the superantigen-induced T cell response in the spleen, and macrophage-depleted animals exhibited overall the same magnitude and kinetics of SEB-mediated T cell activation and anergy-induction as their nondepleted counterparts. Our data thus exclude an essential role of peripheral macrophages or macrophage-secreted cytokines in the systemic T cell activation caused by bacterial superantigens in vivo.