Human mast cells present antigen to autologous CD4+ T Cells

Publication date: Available online 15 June 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Sahar Lotfi-Emran, Brant R. Ward, Quang T. Le, Andrea L. Pozez, Masoud H. Manjili, Judith Woodfolk, Lawrence B. Schwartz
BackgroundMast cells (MCs), the primary effector cell of the atopic response, participate in immune defense at host/environment interfaces, yet the mechanisms by which they interact with CD4⁺-T cells has been controversial.ObjectiveWe utilize in situ-matured primary human MCs and matched CD4⁺-T cells to diligently assess the ability of MCs to act as antigen-presenting cells.MethodsWe examined mature human skin-derived MCs by flow cytometry for expression of antigen-presenting molecules; for their ability to stimulate CD4⁺-T cells to express CD25 and proliferate when exposed to superantigen or to CMV antigen using matched T cells and MCs from CMV seropositive or seronegative donors; and for uptake of antigens. Subcellular localization of antigen, HLA molecules and tryptase was analyzed by structured illumination microscopy.ResultsOur data show that IFNγ induces Human Leukocyte Antigen (HLA) class II, HLA-DM, CD80, and CD40 expression on MCs, while MCs take up soluble and particulate antigens in an IFNγ-independent manner. IFNγ-primed MCs guide activation of T cells by S. aureus superantigen, and when pre-incubated with cytomegalovirus (CMV) antigens induce a recall CD4⁺-Th1 proliferation response only in CMV-seropositive donors. MCs co-opt their secretory granules for antigen processing and presentation. Consequently, MC degranulation increases surface delivery of HLA class II:peptide, further enhancing stimulation of T cell proliferation.ConclusionsIFNγ primes human MCs to activate T cells via superantigen and to present CMV antigen to Th1 cells, co-opting MC secretory granules for antigen processing and presentation, and creating a feed-forward loop of T cell-MC cross-activation.

Graphical abstract

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