| First Author | Rogers MC | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 4 | Pages | 1253-1266 |
| PubMed ID | 29997123 | Mgi Jnum | J:264320 |
| Mgi Id | MGI:6195401 | Doi | 10.4049/jimmunol.1800096 |
| Citation | Rogers MC, et al. (2018) CD4(+) Regulatory T Cells Exert Differential Functions during Early and Late Stages of the Immune Response to Respiratory Viruses. J Immunol 201(4):1253-1266 |
| abstractText | 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 after inoculation. These results indicate that the presence of Tregs at inoculation is critical for efficient priming of the CD8(+) T cell response to ARI, whereas later in infection, Tregs are dispensable for virus clearance. |
