Bridging the gap : CD8αß+ γδ T cells at the frontline of neonatal respiratory immunity 2259032

Abstract Introduction The observation that infants are more susceptible to some pathogens but resistant to others has long puzzled our understanding of early life immunity. This dichotomy can be explained by the absence or presence of specific immune components during this developmental period. Here we describe a population of CD8αß+ γδ T cells that are highly represented in the lungs of neonatal mice and assess their contribution to respiratory antiviral immunity. Methods Adult Foxn1α”/α” mutant mice, which harbor a persistently late fetal thymus, and C57BL/6 neonatal mice were used to assess respiratory perinatal T cells via intravascular labeling and flow cytometry. IFNγ production after in vitro αCD3/CD28 or inflammatory cytokine (IL-12/18) stimulation was determined. Mice were also infected with influenza virus and monitored for weight loss, viral load, and T cell activation by flow cytometry. Results Naïve Foxn1α”/α” mice harbored more CD8αß+ γδ T cells in their lung parenchyma compared to Foxn1α”/+ mice. These cells produce IFNγ and are particularly reactive to cytokine stimulation. While CD8αß+ γδ T cells account for 25% of the T cells in the lungs of C57BL/6 pups at post-natal day 0 (P0), their representation declines by P7. Interestingly, P3 pups express the activation marker CD69 48 h after influenza infection. Since Foxn1α”/α” mice are enriched for CD8αß+ γδ T cells and generate few conventional αß T cells, we infected them with influenza to determine whether the CD8αß+ γδT cells were sufficient for protection. Interestingly, Foxn1α”/α” mice were acutely resistance to influenza before eventually succumbing to a persistent infection. Conclusion CD8αß+ γδ T cells are a population of IFNγ producers enriched in the neonatal lung and activated early after influenza infection. We posit these are innate-like T cells unique to the perinatal period and poised to temporarily fill the functional niche of bona fide tissue resident memory T cells, which are lacking in the neonate. Funding Source NIH/NAID Grant# P01AI139449 Topic Categories Mucosal and Regional Immunology (MUC)