title: Human mast cells costimulate T cells through a CD28-independent interaction.
abstract: Mast cells are innate immune cells usually residing in peripheral tissues, where they are likely to activate T-cell responses. Similar to other myeloid immune cells, mast cells can function as antigen-presenting cells. However, little is known about the capacity of human mast cells to costimulate CD4(+) T cells. Here, we studied the T-cell stimulatory potential of human mast cells. Peripheral blood derived mast cells were generated and cocultured with isolated CD4(+) T cells. In the presence of T-cell receptor triggering using anti-CD3, mast cells promoted strong proliferation of T cells, which was two- to fivefold stronger than the "T-cell promoting capacity" of monocytes. The interplay between mast cells and T cells was dependent on cell-cell contact, suggesting that costimulatory molecules on the mast cell surface are responsible for the effect. However, in contrast to monocytes, the T-cell costimulation by mast cells was independent of the classical costimulatory molecule CD28, or that of OX40L, ICOSL, or LIGHT. Our data show that mast cells can costimulate human CD4(+) T cells to induce strong T-cell proliferation, but that therapies aiming at disrupting the interaction of CD28 and B7 molecules do not inhibit mast cell mediated T-cell activation.
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Jolien
authors: J
authors: Suurmond
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Annemarie L
authors: AL
authors: Dorjée
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Tom W J
authors: TW
authors: Huizinga
authors: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors: René E M
authors: RE
authors: Toes
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D053278:OX40 Ligand / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D018106:CD28 Antigens; C498514:ICOSLG protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D053278:OX40 Ligand; D011948:Receptors, Antigen, T-Cell; C089251:TNFSF4 protein, human
keywords: CD28 antigens; CD4 positive T lymphocytes; Costimulation; Mast cells; T-cell proliferation