Neonatal CD4+ T cells have a characteristic transcriptome and epigenome and respond to TCR stimulation with proliferation and yet a limited immune response.

The adaptive immune response is coordinated by CD4+ T cells, which determine the type and strength of the immune response and the effector cells involved. It has been reported that CD4+ T cells are less responsive in neonates, leading to low activation of the cellular response and poor antibody production by B cells. This low response is essential for the tolerant window that favors birth transition from the sterile environment in the womb to the outside world but leaves neonates vulnerable to infection, which is still an important health issue.

IL-12 Signaling Contributes to the Reprogramming of Neonatal CD8 T Cells.

Neonates are highly susceptible to intracellular pathogens, leading to high morbidity and mortality rates. CD8 T lymphocytes are responsible for the elimination of infected cells. Understanding the response of these cells to normal and high stimulatory conditions is important to propose better treatments and vaccine formulations for neonates.

Cooperation between T cell receptor and Toll-like receptor 5 signaling for CD4 T cell activation.

CD4 T cells recognize antigens through their T cell receptors (TCRs); however, additional signals involving costimulatory receptors, for example, CD28, are required for proper T cell activation. Alternative costimulatory receptors have been proposed, including members of the Toll-like receptor (TLR) family, such as TLR5 and TLR2. To understand the molecular mechanism underlying a potential costimulatory role for TLR5, we generated detailed molecular maps and logical models for the TCR and TLR5 signaling pathways and a merged model for cross-interactions between the two pathways.

Protein complexes associated with β-catenin differentially influence the differentiation profile of neonatal and adult CD8 T cells.

The canonical Wnt signaling pathway is a master cell regulator involved in CD8 T cell proliferation and differentiation. In human CD8 T cells, this pathway induces differentiation into memory cells or a "stem cell memory like" population, which is preferentially present in cord blood. To better understand the role of canonical Wnt signals in neonatal or adult blood, we compared the proteins associated with β-catenin, in nonstimulated and Wnt3a-stimulated human neonatal and adult naive CD8 T cells.

CD8 T Cells from Human Neonates Are Biased toward an Innate Immune Response.

To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8 T cells with that of their adult counterparts. We found that neonatal lymphocytes have a distinct epigenomic landscape associated with a lower expression of genes involved in T cell receptor (TCR) signaling and cytotoxicity and a higher expression of genes involved in the cell cycle and innate immunity. Functional studies corroborated that neonatal CD8 T cells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species.