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) beta-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 V beta 8+ 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.
First Department of Medicine, University of Mainz, Germany.
M
M
Koesling
O
O
Rott
B
B
Fleischer
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division; D017635:Clonal Anergy / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; C031818:enterotoxin B, staphylococcal