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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
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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 4

MC-dependent recruitment, proliferation, and activation of γδ T cells at sites of DENV infection.

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MC-dependent recruitment, proliferation, and activation of γδ T cells at...
WT and Sash mice were injected with CFSE 4 hours before s.c. FP injection of 1 × 105 pfu DENV or saline. (A) FPs and (B) DLNs were collected 24 hours after infection, and CFSE+ and CFSE– γδ T cells were enumerated by flow cytometry. Sash mice showed significantly reduced numbers of both CFSE+ and CFSE– γδ T cells in FPs compared with WT mice. Representative histograms showing CFSE detection in CD4+, CD8+, and γδ T cell subsets in the DLNs of (C) uninfected and (D) infected WT mice. γδ T cells but not CD4+ or CD8+ T cells migrated to the DLNs from the site of infection. Multiple peaks in the histogram indicate proliferation of γδ T cells. Recruitment of T cells in the (E) FPs and (F) DLNs upon infection in WT but not Sash mice was confirmed by injecting CFSE-labeled splenocytes 24 hours prior to infection and analyzing the CFSE+ T cell numbers in FPs and DLNs 24 hours after infection. (G–I) Single-cell suspensions of LN cells, collected 24 hours and 48 hours after infection, were treated with monensin for 6 hours and then stained for the surface markers CD3, CD4, CD8, and γδ TCR and intracellularly for IFN-γ. Total numbers of IFN-γ–producing cells in WT, Sash, and Sash-R mice were subtyped on the basis of (G) γδ, (H) CD8+, and (I) CD4+ T cells. Data represent the mean ± SEM. *P < 0.05, **P < 0.01, and ****P < 0.0001, by 2-way ANOVA with Sidak’s multiple comparisons test. n = 3–6 mice per group.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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