Airway CD8⁺T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Abstract

Infants and young children are disproportionately susceptible to severe complications from respiratory viruses, although the underlying mechanisms remain unknown. Recent studies show that the T cell response in the lung is important for protective responses to respiratory infections, although details on the infant/pediatric respiratory immune response remain sparse. The objectives of the present study were to characterize the local versus systemic immune response in infants and young children with respiratory failure from viral respiratory tract infections and its association to disease severity. Daily airway secretions were sampled from infants and children 4 years of age and younger receiving mechanical ventilation owing to respiratory failure from viral infection or noninfectious causes. Samples were examined for immune cell composition and markers of T cell activation. These parameters were then correlated with clinical disease severity. Innate immune cells and total CD31 T cells were present in similar proportions in airway aspirates derived from infected and uninfected groups; however, the CD8:CD4 T cell ratio was markedly increased in the airways of patients with viral infection compared with uninfected patients, and specifically in infected infants with acute lung injury. T cells in the airways were phenotypically and functionally distinct from those in blood with activated/memory phenotypes and increased cytotoxic capacity. We identified a significant increase in airway cytotoxic CD81 T cells in infants with lung injury from viral respiratory tract infection that was distinct from the T cell profile in circulation and associated with increasing disease severity. Airway sampling could therefore be diagnostically informative for assessing immune responses and lung damage.

Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection

“…Experimental RSV infection of adult humans revealed that greater frequencies of virus-specific CD8 T cells in the BAL correlated with reduced clinical disease symptoms [57]. In contrast, a greater ratio of CD8 to CD4 T cells in the airways is associated with acute lung injury during common respiratory tract infections such as RSV [58].…”

COVID-19 pathophysiology: A review

“…Whether the appearance of pathological T cells in adult patients with severe COVID-19 diseases is due to the compensation for this fundamental aging process or not is unclear. At the early stage after birth, CD4 + T cells are impaired in production of Th1 associated proinflammatory cytokines and skewed toward Th2 (67). CD8 + T cells reduced expression of cytotoxic and inflammatory mediators.…”

Dissecting the defects in the neonatal CD8+ T-cell response

“…Increased T‐cell production of ROS, coupled with neonates’ diminished free‐radical scavenging capabilities, damages the lung . Prolonged recruitment and survival of neutrophils due to increased IL‐8 from neonatal T cells plays a role in tissue damage in the lungs . Infants who develop acute lung injury have been shown to have a higher level of IL‐6 and increased CD8:CD4 ratio in the lung during injury and infection …”

“…99 Prolonged recruitment and survival of neutrophils due to increased IL-8 from neonatal T cells plays a role in tissue damage in the lungs. 97,100 Infants who develop acute lung injury have been shown to have a higher level of IL-6 and increased CD8:CD4 ratio in the lung during injury and infection. 100…”