Characterization of the Functional and Phenotypic Profile of a Naïve Conventional Innate-like Population of CD8+ T Cells in Neonatal Cord Blood 2260244

Abstract Introduction 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. Funding Source U24AI152176 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)