(509) Characterization of the Functional and Phenotypic Profile of a Naïve Conventional Innate-like Population of CD8+ T Cells in Neonatal Cord Blood

Introduction/Rationale: Neonates, while highly susceptible to serious infections, may harbor unique features of adaptive immunity that protect during infancy before durable memory is established. Previous work in our lab has identified a naive conventional CD8+ T cell population, which we termed fetal innate-like T cells (FITs), that is unique to cord blood (CB) and shares phenotypic features with innate-like unconventional T cells and NK cells. This FIT population is defined by co-expression of KLRG1, CD161 and CD8αβ, but more investigation is needed to identify their overlapping and distinct functionality with respect to conventional and innate CD8α+ T cells. We hypothesize that FITs share functions with innate lymphoid cells, including cytotoxic mediators and cytokines, that provide alternative paths to protection in the neonatal period.

Methods: To test our hypothesis, we performed high dimensional spectral flow and automated clustering to compare phenotypic and functional profiles of in vitro-stimulated FITs and non-FITs populations from neonates and adults.

Results: Upon stimulation, FITs showed increased expression of either TNFα or Granzyme K, and there were no detectable dual-staining cells. FITs were negative for IFNγ, IL8, and IL17A. FITs could be further distinguished from other conventional CD8+ events by their CD337 (NKp30) expression, a marker more often associated with anti-tumor activity in natural killer cells.

Conclusion: These findings support the presence of a unique subpopulation of conventional CD8αβ T cells that overlap with innate-like lymphoid populations, raising their potential for alternative pathways to protection or immunopathology during early life.