Identifying the immunological drivers of early life homing of human naive T cells

Abstract

Naïve T cells are generally considered as a circulating, homogeneous and quiescent population of T cells. However, recent advancements show that the naïve T cell pool is much more heterogeneous and compartmentalized than thought before. This compartmentalization suggests selective homing of naïve T cells to specific tissues in the body, through the expression of homing markers. Homing of naïve T cells is thought to take place especially early in life. Until this day, the drivers of early-life homing and homing marker expression of naïve T cells are not yet fully understood. In this report, we investigate the immunological context of early life naïve T cell homing. For this purpose, we studied naïve T cell homing throughout early life immune development as well as in response to immunological triggers. First, we analyzed flow cytometry data of the immune system of preterm infants in the first 42 days postpartum. We show that preterm neonates have a high percentage of naïve T cells and that these T cells predominantly express gut homing markers integrin α4β7 and CCR9. Interestingly, the neonatal naïve T cell phenotype does not consistently change within the first 42 days postpartum. Second, we looked at the effect of Toll-Like Receptor (TLR) ligand exposure in different stimulatory settings. TCR and TLR co-stimulation seems to enhance naïve T cell proliferation, along with upregulation of homing markers. Altogether, we conclude that neonatal naive T cells indeed express homing markers and that this is influenced by immune development as well as TCR and TLR stimulation.