CD4+ Regulatory T Cells Exert Differential Functions during Early and Late Stages of the Immune Response to Respiratory Viruses

The Journal of Immunology : Official Journal of the American Association of Immunologists
Meredith C RogersJohn V Williams

Abstract

Acute respiratory virus infection (ARI) induces CD8+ T cells with diminished cytokine production and functional impairment. The role of cellular mediators of immune impairment, specifically CD4+ regulatory T cells (Tregs), is incompletely understood in ARI. Tregs are known suppressors of effector T cell function, but whether they are detrimental or beneficial in ARI remains controversial. We show in this paper that Treg depletion leads to increased CD8+ T cell function and lower virus titer in mice infected with human metapneumovirus. We further demonstrate that Tregs play a temporal role in the immune response to human metapneumovirus and influenza: Treg depletion before infection pathologically reduces virus-specific CD8+ T cell numbers and delays virus clearance, whereas depletion 2 d postinoculation enhances CD8+ T cell functionality without reducing virus-specific CD8+ T cell numbers. Mechanistically, Treg depletion during immune priming led to impaired dendritic cell and CD8+ T cell migration. Further, early Treg depletion was associated with immune skewing toward a type 2 phenotype characterized by increased type 2 innate lymphoid cells and TH2 CD4+ T cells, which was not observed when Treg depletion was delayed until af...Continue Reading

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Citations

Jul 28, 2018·Annual Review of Virology·Meredith C Rogers, John V Williams
May 20, 2020·Viruses·Marlies Ballegeer, Xavier Saelens
Dec 18, 2021·Seminars in Respiratory and Critical Care Medicine·Tom D Y ReijndersTom van der Poll

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