Regulatory T cells are essential to promote proper CD4 T-cell priming upon mucosal infection

A. G. Soerens, A. Da Costa, J. M. Lund

Research output: Contribution to journalArticlepeer-review

Abstract

Regulatory T cells (Tregs) limit autoimmunity and immunopathology using a variety of suppressive mechanisms, but their roles during pathogen-directed immune responses remain unclear. Following herpes simplex virus-2 (HSV-2) infection, mice lacking Tregs fail to control viral replication, pointing to a role for Tregs in facilitating productive immune responses. Using adoptive transfer of T-cell receptor transgenic CD4 T cells into Treg-sufficient or Treg-depleted mice prior to HSV-2 infection, we found that Tregs are required for timely accumulation of HSV-2-specific CD4 T cells within the infected tissues. Further, Tregs are critical for appropriate trafficking of dendritic cells (DCs) from the vaginal mucosa to the draining lymph nodes, which results in fully effective CD4 T-cell priming, activation, and ultimately migration to the infected tissues. Using CTLA-4 conditional knockout mice, we demonstrate that Tregs impact DC migration through a CTLA-4-mediated mechanism. Together, our data highlight the critical role of Tregs in proper potentiation of adaptive immune responses to microbial infection.

Original languageEnglish (US)
Pages (from-to)1395-1406
Number of pages12
JournalMucosal Immunology
Volume9
Issue number6
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Society for Mucosal Immunology.

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