Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF.
We recently reported that mast cells stimulated via FcepsilonRI aggregation can enhance T cell activation by a TNF-dependent mechanism. However, the molecular mechanisms responsible for such IgE-, Ag- (Ag-), and mast cell-dependent enhancement of T cell activation remain unknown. In this study we showed that mouse bone marrow-derived cultured mast cells express various costimulatory molecules, including members of the B7 family (ICOS ligand (ICOSL), PD-L1, and PD-L2) and the TNF/TNFR families (OX40 ligand (OX40L), CD153, Fas, 4-1BB, and glucocorticoid-induced TNFR). ICOSL, PD-L1, PD-L2, and OX40L also are expressed on APCs such as dendritic cells and can modulate T cell function. We found that IgE- and Ag-dependent mast cell enhancement of T cell activation required secreted TNF; that TNF can increase the surface expression of OX40, ICOS, PD-1, and other costimulatory molecules on CD3(+) T cells; and that a neutralizing Ab to OX40L, but not neutralizing Abs to ICOSL or PD-L1, significantly reduced IgE/Ag-dependent mast cell-mediated enhancement of T cell activation. These results indicate that the secretion of soluble TNF and direct cell-cell interactions between mast cell OX40L and T cell OX40 contribute to the ability of IgE- and Ag-stimulated mouse mast cells to enhance T cell activation.
Nakae
Susumu
S
Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
Suto
Hajime
H
Iikura
Motoyasu
M
Kakurai
Maki
M
Sedgwick
Jonathon D
JD
Tsai
Mindy
M
Galli
Stephen J
SJ
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000145:classification / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007073:Immunoglobulin E / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008407:Mast Cells / Q000378:metabolism* / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D053278:OX40 Ligand; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000145:classification / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D018124:Receptors, Tumor Necrosis Factor; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D007073:Immunoglobulin E