Dynamic Circulating T Cell Activation States in Extremely Premature Infants

Abstract Text: Extremely premature infants (EPI) are susceptible to infections and inflammatory diseases. To define peripheral T cell ontogeny in EPI serial blood samples obtained in the first 2 months of life were compared to cord blood from term and preterm infants and healthy adults. We analyzed phosphoprotein expression (CyTOF) and transcriptome(scRNAseq). Differences in T cell abundance, phosphoprotein expression, transcriptome, and clonality were noted. Naïve CD4 and regulatory T cells peaked at 1 month, while naïve CD8 T cells continuously increased. Central memory (CM) CD4 T cells were detected in cord blood and decreased from birth to 1 month. Meanwhile, effector memory (EM) CD4 and CD8 T cells were low at birth and increased by two months of age. scRNAseq demonstrated an expansion of cycling T cells at 1 and 2 months of age and clonal expansion in memory CD8 T cells. PI3K/mTOR pathway (pS6) was suppressed at 1 month and increased at 2 months of age in memory T cell populations. TCR activation (pZAP70) was high in naïve and CM CD4 and CD8 populations concomitant with high dendritic cell activation as measured by HLA-DR, pCREB, and pMAPK, suggesting ongoing antigen presentation and memory T cell generation. pSTAT5 levels increased at 1 and 2 months of age consistent with more cycling T cells. In EPI, there is a dynamic progression of T cell signaling, transcriptome and clonality demonstrating activation, proliferation, antigen presentation, and memory formation. Thus, even very preterm infants can mount antigen-specific adaptive immune responses early in life.