Investigating the impact of CD8+ TRM-mediated protection on the development of secondary immunity following respiratory virus transmission Restricted; Files Only

Abstract

CD8+ tissue-resident memory T cells (TRM) are essential for defending barrier tissues against pathogens. We previously demonstrated their ability to prevent productive infections and severely limit viral spread in a mouse model of parainfluenza virus transmission. However, it is uncertain whether TRM can provide long-term protection in the face of multiple viral exposures. To investigate this, contact mice were immunized to establish Sendai virus (SeV)-specific CD8+ TRM prior to cohousing with a naïve index mouse acutely infected with luciferase-tagged SeV. Post-transmission, contact mice were classified based on the level of SeV replication observed and examined for the development of de novo SeV-specific responses. Additional cohorts were rested for 4 months after transmission before re-exposure to assess how the level of TRM-mediated protection from the initial exposure impacted secondary protection. Our findings show that mice with near-sterilizing T cell immunity during the first exposure failed to induce de novo CD4+ T cell and antibody responses and were more susceptible to secondary exposures months later. These results suggest that intermediate levels of TRM-mediated immunity may provide optimal long-term protection.

Table of Contents

Table of Contents

Introduction                                                                                                                                     1

Methods                                                                                                                                           7

Results                                                                                                                                           11

Figure 1.  PR8 SenNP WT Intranasal Priming Alters Virus Transmission Levels          13

           Figure 2. Prior Transmission Provides Protection Upon Rechallenge.                            16

           Figure 3. Increased NC CD8 TRM in Intermediate Infections Post-Rechallenge.          18

           Figure 4. B Cell Deficiency impairs Long-Term Protection.                                          21                                                                                                     

Discussion                                                                                                                                    22

Future Directions                                                                                                                           25

References                                                                                                                                     27

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Molecular Biology, Cell
Keyword	Immunology CD8+TRM
Committee Chair / Thesis Advisor	Jacob Kohlmeier, Emory University
Committee Members	Alison Kohlmeier, Emory University Rustom Antia, Emory University

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