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

• Published in: The Journal of immunology (1950) 2018-07, Vol.201 (2), p.432-439
• Main Authors: Connors, Thomas J, Baird, J Scott, Yopes, Margot C, Zens, Kyra D, Pethe, Kalpana, Ravindranath, Thyyar M, Ho, Siu-Hong, Farber, Donna L
• Format: Article
• Language: English
• Subjects: Adult; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell differentiation; Child; Child, Preschool; Children; Effector cells; Female; Humans; Immunologic Memory - immunology; Immunological memory; Infant; Infant, Newborn; Infants; Infections; Lung - immunology; Lung - virology; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; Memory cells; Morbidity; Neonates; Pediatrics; Respiratory tract; Respiratory tract diseases; Respiratory tract infection; Respiratory Tract Infections - immunology; Respiratory Tract Infections - virology; Transcription Factors - immunology; Virus Diseases - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1800396

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.