Human mast cells present antigen to autologous CD4+ T cells

Sahar Lotfi-Emran, Brant R. Ward, Quang T. Le, Andrea L. Pozez, Masoud H. Manjili, Judith A. Woodfolk, Lawrence B. Schwartz

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background Mast 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. Objective We used in situ–matured primary human MCs and matched CD4+ T cells to diligently assess the ability of MCs to act as antigen-presenting cells. Methods We examined mature human skin-derived MCs using 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 cytomegalovirus (CMV) antigen using matched T cells and MCs from CMV-seropositive or CMV-seronegative donors, and for antigen uptake. Subcellular localization of antigen, HLA molecules, and tryptase was analyzed by using structured illumination microscopy. Results Our data show that IFN-γ induces HLA class II, HLA-DM, CD80, and CD40 expression on MCs, whereas MCs take up soluble and particulate antigens in an IFN-γ–independent manner. IFN-γ–primed MCs guide activation of T cells by Staphylococcus aureus superantigen and, when preincubated with 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. Conclusions IFN-γ primes human MCs to activate T cells through 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.

Original languageEnglish (US)
Pages (from-to)311-321.e10
JournalJournal of Allergy and Clinical Immunology
Volume141
Issue number1
DOIs
StatePublished - Jan 2018

Keywords

  • CD80
  • HLA class II
  • HLA-DM
  • Mast cell
  • antigen presentation
  • cytomegalovirus antigen
  • structured illumination microscopy
  • superantigen
  • tryptase

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