Asset Details
Do you wish to reserve the book?
Investigating Naïve CD8+ T Cells’ Heterogeneity in Early Life
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Investigating Naïve CD8+ T Cells’ Heterogeneity in Early Life
Do you wish to request the book?
Investigating Naïve CD8+ T Cells’ Heterogeneity in Early Life
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Dissertation
Investigating Naïve CD8+ T Cells’ Heterogeneity in Early Life
2025
Overview
The question of why human infants appear to have weaker immune responses compared to adults has long puzzled immunologists. The perinatal period involves considerable vulnerability to infectious illness, yet a newer model of early life immunity seeks to describe the features and functions unique to this period to better understand the adaptations that may already help to protect neonates. Recent decades of work have shown that the adaptive immune system possesses many innate-like features and that an array of unconventional T cells with atypical reactivities and functions are generated during fetal development and throughout the lifespan. We built upon earlier reports that human umbilical cord blood contains circulating T cells that express innate-like surface markers and a possess a limited cytokine profile following activation and sought to identify their distinguishing characteristics. Here, we show that cord blood contains multiple immunologically naïve CD8+ αβ T cell populations, including a population of fetally-derived and innate-like CD8+ T cells (FITs) marked by expression of KLRG1 and CD161 but lacking important characteristics of other well-described unconventional populations. We hypothesized that this population would harbor unique transcriptomic features relative to other infant and adult conventional naïve and innate-like T cells and used their unique phenotype to enrich for FITs as well as other lymphocyte populations for single cell sequencing. We found that FITs were a clonally diverse population that could be further distinguished from infant recent thymic emigrant CD8+ αβ T cells by their expression of innate-like surface markers and a conserved set of genes related to type 17 immunity and tissue homing. While FITs did not appear capable of in vitro IL-12/IL-18-mediated bystander activation, they produced TNF but not IL-8 following PMA/ionomycin stimulation and were competent to upregulate IRF4 similar to adult CD8+ T cells following TCR-dependent stimulation. These findings suggest that FITs may play a role in human tissue-specific perinatal immunity and should be further studied in this context to explore potentially novel protective immune mechanisms deployed by neonates.
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9798293841950
