Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Defining the role of CD4+ T cells during human metapneumovirus infection

Lamens, Kristina (2019) Defining the role of CD4+ T cells during human metapneumovirus infection. Master's Thesis, University of Pittsburgh. (Unpublished)

This is the latest version of this item.

[img] PDF
Restricted to University of Pittsburgh users only until 21 October 2021.

Download (1MB) | Request a Copy

Abstract

Human metapneumovirus (HMPV) is a leading cause of respiratory tract infection in pediatric, elderly, and immunocompromised populations. Clearance of respiratory viruses like HMPV rely primarily on the destruction of infected cells by cytotoxic CD8+ T cells. However, signals provided by CD4+ helper T cells significantly impact the magnitude and effectiveness of CD8+ T cells. Despite HMPV being an important human pathogen, the role of CD4+ helper T cells in the immune response to HMPV is largely unknown. Using a C57BL/6 mouse model of acute infection, we identified an immunodominant CD4+ T cell epitope in the viral nucleoprotein and constructed the first MHC-II tetramer for HMPV. Analysis of pulmonary T cells revealed that virus-specific cells were most abundant on day 10 post-infection and were TH1-skewed. Additionally, virus-specific CD4+ T cells displayed phenotypic and functional markers of impairment, including inhibitory receptor co-expression and prolonged PD-1 upregulation. To determine the contribution of CD4+ T cells to the CD8+ T cell response, CD4+ T cells were antibody-depleted prior to HMPV infection. Depletion of CD4+ T cells led to delayed viral clearance and enhanced PD-1 expression on virus-specific CD8+ T cells. We also investigated the importance of CD40/CD40L signaling as a mechanism of CD4+ T cell help and demonstrate that either enhancing or blocking this pathway is detrimental in the context of HMPV infection. Further characterization of virus-specific CD4+ helper T cells, their regulation by PD-1, and their role in CD8+ T cell impairment will provide new insights that aid in the design of effective vaccines for HMPV.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lamens, Kristinakdl24@pitt.edukdl240000-0002-2582-8010
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKane, Lawrencelkane@pitt.edu
Committee MemberMcElroy, Anitamcelroya@pitt.edu
Committee MemberHand, Timothytimothy.hand@chp.edu
Committee MemberAlcorn, Johnjohn.alcorn@chp.edu
Thesis AdvisorWilliams, Johnjvw@pitt.edu
Date: 21 October 2019
Date Type: Publication
Defense Date: 1 October 2019
Approval Date: 21 October 2019
Submission Date: 4 October 2019
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 59
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Microbiology and Immunology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: respiratory virus, HMPV, CD4+ T cells
Date Deposited: 21 Oct 2019 15:22
Last Modified: 21 Oct 2019 15:22
URI: http://d-scholarship.pitt.edu/id/eprint/37699

Available Versions of this Item


Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item