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Immune synapses between mast cells and γδ T cells limit viral infection
Chinmay Kumar Mantri, Ashley L. St. John
Chinmay Kumar Mantri, Ashley L. St. John
Published February 4, 2019; First published December 18, 2018
Citation Information: J Clin Invest. 2019. https://doi.org/10.1172/JCI122530.
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Categories: Research Article Immunology Infectious disease

Immune synapses between mast cells and γδ T cells limit viral infection

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Abstract

Mast cells (MCs) are immune sentinels, but whether they also function as antigen-presenting cells (APCs) remains elusive. Using mouse models of MC deficiency, we report on MC-dependent recruitment and activation of multiple T cell subsets to the skin and draining lymph nodes (DLNs) during dengue virus (DENV) infection. Newly recruited and locally proliferating γδ T cells were the first T cell subset to respond to MC-driven inflammation, and their production of IFN-γ was MC dependent. MC–γδ T cell conjugates were observed consistently in infected peripheral tissues, suggesting a new role for MCs as nonconventional APCs for γδ T cells. MC-dependent γδ T cell activation and proliferation during DENV infection required T cell receptor (TCR) signaling and the nonconventional antigen presentation molecule endothelial cell protein C receptor (EPCR) on MCs. γδ T cells, not previously implicated in DENV host defense, killed infected targeted DCs and contributed to the clearance of DENV in vivo. We believe immune synapse formation between MCs and γδ T cells is a novel mechanism to induce specific and protective immunity at sites of viral infection.

Authors

Chinmay Kumar Mantri, Ashley L. St. John

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Figure 6

Immunological synapse formation between MCs and γδ T cells at infection sites.

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Immunological synapse formation between MCs and γδ T cells at infection ...
Mice (n = 3) were injected with (A and B) saline or (C–E) 1 × 105 pfu DENV. FP tissue collected 24 hours after infection was sectioned and stained for blood vessels (CD31, blue) and the γδ TCR (green) and then probed for MC-heparin (MC granules, red). Representative control confocal images in which MCs can be viewed near blood vessels (A) without nearby γδ T cells or (B) in which γδ T cells appeared infrequently in the same field as MCs. The area in the gray box is enlarged as an inset in B, and white a arrowhead indicates γδ T cells. (C) In DENV-infected tissues, several γδ T cells clustered around MCs that appeared activated because of MC granules that were extracellular in the tissue (indicated by white arrowheads in the enlarged inset on the right). (D) Many γδ T cells formed close contacts with MCs in DENV-infected tissues. Quantification of MC–γδ T cell contacts and additional representative images are provided in Supplemental Figure 13. (E) MCs and γδ T cells were observed interacting in the peritoneal cavity 24 hours after i.p. infection with DENV (1 × 106 pfu). Peritoneal lavage cells were cytospun onto glass slides prior to staining with antibodies against CD3, γδ TCR, and tubulin and probing against MC-heparin. MCs and γδ T cells appeared to form stable contacts that were visualized after isolation. Strong polarization of CD3 and γδ TCR toward the MC contact site revealed immune synapse formation. (F) No stable contacts between MCs and γδ T cells were observed in cytospins from similarly prepared uninfected peritoneal cells. Additional representative images of MC–γδ T cell conjugates in cytospins from DENV-infected mice and of control cytospins are provided in Supplemental Figure 14. Scale bars: 20 μm; 20 μm (enlarged insets in B–F).
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Copyright © 2019 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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