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Title: The Effects of Cytokine Signaling and Memory Differentiation on Mammalian T-helper Cell Effector Phenotype Plasticity
Authors: Heilbronner, Alison
Advisors: Graham, Andrea L.
Department: Molecular Biology
Certificate Program: Global Health and Health Policy Program
Class Year: 2020
Abstract: T-helper (Th) cells polarize towards different effector phenotypes, including Type 1 and Type 2, which coordinate the defense against different classes of pathogens. However, Th cells can also exhibit plasticity (i.e., alter effector phenotypes) when conditions change. The coordination of the immune system into different effector phenotypes is made possible via cytokine signaling. This effector phenotype polarization occurs concurrently with Th cell memory differentiation. Although both memory differentiation and cytokine signaling affect Th cell effector phenotype plasticity independently, the interaction between the two, and the resultant effects on plasticity, have never been studied. Here I show Th cell plasticity is concurrently affected by memory phenotype and cytokine signaling. By simultaneously manipulating intercellular communication and phenotyping Th cells, my controlled in vitro studies show that cytokine signaling and memory status have dissimilar impacts on the plasticity of cells that are initially biased Type 1 then subsequently biased Type 2 (“Th1 \(\rightarrow\) Th2”) versus cells biased Th2 \(\rightarrow\) Th1. Cytokine signaling increases Th1 \(\rightarrow\) Th2 effector Th cell plasticity. However, cytokine signaling impedes Th2 \(\rightarrow\) Th1 memory precursor Th cell plasticity. These results demonstrate how signaling and differentiation factors interact to affect Th cell plasticity. This interaction emphasizes the importance of considering these factors when designing vaccines and treating coinfections. In both cases, Th cell effector phenotype polarization and plasticity must be carefully manipulated. My work suggests that such manipulation depends on the cytokine environment and memory status distribution of Th cells, which is unique to each patient.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Molecular Biology, 1954-2022
Global Health and Health Policy Program, 2017-2022

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