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(Unpublished)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Unpublished |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