Virus-specific Tregs are terminally differentiated upon peripheral activation and dependent on thymic output after both primary and secondary infection (P1035)
Abstract
<jats:title>Abstract</jats:title>
<jats:p>Regulatory CD4 T cells (Tregs) are defined as FoxP3+ cells and are categorized as natural (nTreg) or induced (iTreg). iTregs can be further classified as pathogen or epitope specific (pTreg). pTregs can share epitope specificity with effector cells (Teffs) and expand in response to infection. Although pTregs reduce infection-induced immunopathology, over-expansion and persistence can have a negative impact on pathogen clearance. Studying CD4 T cell responses to respiratory syncytial virus (RSV) infection, we found that the pTreg response had different dynamics than Teffs, which promoted efficient RSV clearance with minimal immunopathology and effectively established adaptive memory responses. The IA(b)M209-specific pTreg response was subdominant to IA(b)M209-specific Teffs. It peaked early to suppress responses in lymphoid organs after primary infection, but had limited regulation on CD8 T cell responses at the site of infection. The IA(b)M209-specific pTreg response contracted when the specific Teff responses peaked, and was diminished after secondary infection when an adequate adaptive Teff responses were established. The dynamics and differentiation pattern of the IA(b)M209-specific pTreg response was TCR clonotype-specific and enriched for recent thymic immigrants even on secondary infection, which suggests that pTreg responses are recalibrated with each infection to provide an optimal balance of Teff-mediated virus clearance and immunoregulation to limit tissue damage.</jats:p>
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