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T-cell Dependent and independent mechanisms of chlamydial eradication and control

Poston, Taylor (2018) T-cell Dependent and independent mechanisms of chlamydial eradication and control. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Poston, Taylortbp11@pitt.edutbp11
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDarville, Tonilad@email.unc.edu
Committee CoChairRinaldo, Charles Rrinaldo@pitt.eduRINALDO
Committee MemberMailliard, Robbie Brbm19@pitt.eduRBM190000-0001-5501-503X
Committee MemberAlcorn, John F.jfa9@pitt.eduJFA9
Committee MemberLin, Philana Lingpll7@pitt.eduPLL7
Date: 30 January 2018
Date Type: Publication
Defense Date: 16 October 2017
Approval Date: 30 January 2018
Submission Date: 10 October 2017
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 122
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Chlamydia, T-cell, B-cell, immunology, vaccine
Date Deposited: 30 Jan 2018 22:49
Last Modified: 01 Jan 2019 06:15
URI: http://d-scholarship.pitt.edu/id/eprint/33250

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