Superantigen-mediated human monocyte-T lymphocyte interactions are associated with an MHC class II-, TCR/CD3-, and CD4-dependent mobilization of calcium in monocytes.
The present study was designed to examine the potential involvement of calcium ions as second messengers in the mediation of the staphylococcal enterotoxin A (SEA)/MHC class II-induced activation of human monocytes. Treatment of monocytes with a monomeric form of SEA failed to induce detectable changes in the level of intracellular calcium in either monocytes or THP-1 cells. However, cross-linking of SEA with biotin-avidin induced a rapid and transient increase in calcium levels in monocytes and in INF-gamma-treated THP-1 cells. This artificial cross-linking system was reproduced by natural physiologic ligands expressed on the surface of T lymphocytes. Delayed, transient, and concentration (cell as well as toxin)-dependent increases in the cytoplasmic level of free calcium in SEA-treated monocytes were observed upon the addition of autologous resting T cells or purified CD4+ cells, but not of CD8+ cells, B cells, or neutrophils. Antibodies against MHC class II Ag, TCR/CD3, and CD4 molecules inhibited the SEA-dependent interaction between monocytes and T cells as indicated by significant decreases in the rise of calcium levels observed in monocytes. Anti-CD8 and anti-class I antibodies did not affect the interaction between the monocytes and the T cells and failed to alter the calcium response. Taken together, these results suggest that the SEA-induced, T cell-dependent calcium mobilization in monocytes requires physical interactions between SEA-MHC class II, TCR/CD3, and CD4 molecules. The ability to mediate a T cell-dependent calcium increase in monocytes was shared by several enterotoxins including staphylococcal enterotoxin B and toxic shock syndrome toxin-1. The characteristics of the SEA-mediated calcium mobilization in monocytes strongly support the hypothesis that this response is an integral part of the signal transducing machinery linked to MHC class II molecules.
Damaj
B
B
Department of Medicine, Université Laval, Ste. Foy, Québec, Canada.
Mourad
W
W
Naccache
P H
PH
D000942:Antigens, Bacterial / Q000276:immunology*; D015704:CD4 Antigens / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
D000942:Antigens, Bacterial; D015704:CD4 Antigens; D004768:Enterotoxins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; C026066:enterotoxin A, Staphylococcal; D002118:Calcium