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Article ; Online: Regulatory T cells suppress the motility of cytotoxic T cells in Friend retrovirus–infected mice

Daniela Mittermüller / Lucas Otto / Zoë Long / Andreas Kraus / Alexander Beer / Anja Hasenberg / Gennadiy Zelinskyy / Jaana Westmeier / Kim J. Hasenkrug / Ulf Dittmer / Matthias Gunzer

JCI Insight, Vol 8, Iss

2023  Volume 13

Abstract: Antiviral immunity often requires CD8+ cytotoxic T lymphocytes (CTLs) that actively migrate and search for virus-infected targets. Regulatory T cells (Tregs) have been shown to suppress CTL responses, but it is not known whether this is also mediated by ... ...

Abstract Antiviral immunity often requires CD8+ cytotoxic T lymphocytes (CTLs) that actively migrate and search for virus-infected targets. Regulatory T cells (Tregs) have been shown to suppress CTL responses, but it is not known whether this is also mediated by effects on CTL motility. Here, we used intravital 2-photon microscopy in the Friend retrovirus (FV) mouse model to define the impact of Tregs on CTL motility throughout the course of acute infection. Virus-specific CTLs were very motile and had frequent short contacts with target cells at their peak cytotoxic activity. However, when Tregs were activated and expanded in late-acute FV infection, CTLs became significantly less motile and contacts with target cells were prolonged. This phenotype was associated with development of functional CTL exhaustion. Tregs had direct contacts with CTLs in vivo and, importantly, their experimental depletion restored CTL motility. Our findings identify an effect of Tregs on CTL motility as part of their mechanism of functional impairment in chronic viral infections. Future studies must address the underlying molecular mechanisms.
Keywords Immunology ; Virology ; Medicine ; R
Subject code 616
Language English
Publishing date 2023-07-01T00:00:00Z
Publisher American Society for Clinical investigation
Document type Article ; Online
Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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