eprintid: 33250
rev_number: 15
userid: 6843
dir: disk0/00/03/32/50
datestamp: 2018-01-30 22:49:19
lastmod: 2019-01-01 06:15:21
status_changed: 2018-01-30 22:49:19
type: thesis_degree
metadata_visibility: show
contact_email: tbposton@email.unc.edu
eprint_status: archive
creators_name: Poston, Taylor
creators_email: tbp11@pitt.edu
creators_id: tbp11
title: T-cell Dependent and independent mechanisms of chlamydial eradication and control
ispublished: unpub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: public
keywords: Chlamydia, T-cell, B-cell, immunology, vaccine
abstract: Evidence suggests that Th1 cells and antibody are the primary mediators of chlamydial protection. However, the impact of Th1 polyfunctionality and T-cell independent antibody on host protection against Chlamydia has not been fully explored. Using an adoptive transfer approach in the mouse model of Chlamydia muridarum, we investigated the role of transgenic Chlamydia-specific CD4 T cells and naïve, polyclonal B cells in mediating bacterial clearance and conferring resistance to lethality, respectively. We hypothesized that Chlamydia-specific Th1 cells would provide enhanced protection against genital infection compared to a polyclonal repertoire, and that B-cells are required for preventing lethality associated with disseminated infection. We found that polyfunctional, transgenic Th1 cells produced the highest levels of IFN-γ, afforded the greatest reduction in bacterial burden from the genital tract during primary infection, and provided equal protection during secondary infection, compared to the polyclonal T cell response. We also found that B cells and IFN-γ synergize to protect against disseminated infection in the absence of Th1 cells, despite mice developing a chronic genital tract infection. Collectively, these data suggest that polyfunctional, Chlamydia-specific Th1 cells mediate optimal chlamydial clearance from the genital tract, while the T-independent B-cell response is primarily involved in limiting extragenital infection to distal organs. Adoptive transfer studies provide a powerful approach for elucidation of protective correlates of immunity against chlamydial infection that can guide development of rational public health vaccine strategies.
date: 2018-01-30
date_type: published
pages: 122
institution: University of Pittsburgh
refereed: TRUE
etdcommittee_type: committee_chair
etdcommittee_type: committee_cochair
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Darville, Toni
etdcommittee_name: Rinaldo, Charles R
etdcommittee_name: Mailliard, Robbie B
etdcommittee_name: Alcorn, John F.
etdcommittee_name: Lin, Philana Ling
etdcommittee_email: lad@email.unc.edu
etdcommittee_email: rinaldo@pitt.edu
etdcommittee_email: rbm19@pitt.edu
etdcommittee_email: jfa9@pitt.edu
etdcommittee_email: pll7@pitt.edu
etdcommittee_id: RINALDO
etdcommittee_id: RBM19
etdcommittee_id: JFA9
etdcommittee_id: PLL7
etdcommittee_orcid: 0000-0001-5501-503X
etd_defense_date: 2017-10-16
etd_approval_date: 2018-01-30
etd_submission_date: 2017-10-10
etd_release_date: 2018-01-30
etd_access_restriction: 1_year
etd_patent_pending: FALSE
thesis_type: dissertation
degree: PhD
citation:   Poston, Taylor  (2018) T-cell Dependent and independent mechanisms of chlamydial eradication and control.  Doctoral Dissertation, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/33250/1/Poston_Taylor_Dissertation_12_2017.pdf