Expression of immune checkpoint molecules on adult and neonatal T-cells

Area of Science:

• Immunology
• Neonatal Medicine
• Infectious Diseases

Background:

• Neonates, particularly preterm infants, are highly susceptible to serious bacterial infections.
• Neonates also face a higher risk of post-inflammatory diseases, including bronchopulmonary dysplasia and periventricular leukomalacia.
• An impaired ability to resolve inflammation may underlie these increased risks in neonates.

Purpose of the Study:

• To investigate the proliferative response of neonatal T-cells compared to adult T-cells.
• To examine the expression of immune-checkpoint molecules (ICM) and activation markers on neonatal T-cells versus adult T-cells.
• To test the hypothesis that increased neonatal T-cell activation contributes to failed inflammation resolution.

Main Methods:

• Compared proliferative capacity and T-cell activation markers in neonatal and adult T-cells.
• Assessed the expression of immune-checkpoint molecules (ICM), specifically PD-L1, on T-cells.
• Stimulated T-cells using OKT3, Group B Streptococcus (GBS), and Escherichia coli (E. coli).

Main Results:

• Neonatal CD4+ and CD8+ T-cells exhibited increased proliferation and activation markers compared to adult T-cells.
• Neonatal T-cells showed decreased expression of ICM, notably PD-L1, upon stimulation with OKT3 and GBS.
• PD-L1 expression on neonatal T-cells was not decreased after E. coli stimulation; CD3 and CD28 expression did not differ between age groups.

Conclusions:

• Neonatal T-cells possess a heightened proliferative capacity and activation response.
• Reduced expression of immune-checkpoint molecules, particularly PD-L1, on activated neonatal T-cells may impair inflammation resolution.
• This immune dysregulation in neonates could contribute to their increased risk for post-inflammatory conditions.