Developmental Regulation of Effector and Resident Memory T Cell Generation during Pediatric Viral Respiratory Tract Infection

J Immunol. 2018 Jul 15;201(2):432-439. doi: 10.4049/jimmunol.1800396. Epub 2018 May 30.

Abstract

Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm), which provide long-term protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. In this study, we investigated T cell responses in the upper respiratory tract (URT) and lower respiratory tract (LRT) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8+ T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (effector memory RA+ T cells) in the URT and LRT with reduced Trm in the early neonatal period, and decreased effector memory RA+ T cell and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared with adult T cells, suggesting a mechanism for preferential generation of effector over Trm. The developmental regulation of respiratory T cell responses as revealed in the present study is important for diagnosing, monitoring, and treating VRTI in the critical early life stages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunologic Memory / immunology*
  • Infant
  • Infant, Newborn
  • Lung / immunology
  • Lung / virology
  • Lymphocyte Activation / immunology
  • Male
  • Respiratory Tract Infections / immunology*
  • Respiratory Tract Infections / virology
  • Transcription Factors / immunology
  • Virus Diseases / immunology*

Substances

  • Transcription Factors