Date of Award
Doctor of Philosophy
Field of Study
Microbiology and Immunology
Graduate School of Biomedical Sciences
The purpose of these studies was to examine the role of regulatory T cells (Tregs) in mycoplasma respiratory disease. Depletion of Tregs resulted in increased disease severity. Tregdepleted mice lost significantly more weight over the course of the experiment, and displayed a significantly higher incidence of both gross lung lesions and histological lung lesions at day 14 post-infection. Treg depletion resulted in increased cell infiltration into the lungs by day 14 postinfection, and significant increases in the serum levels of mycoplasma-specific antibodies. Treg depletion also led to an increase in the percentage of IL-13+ T cells in the LRNs, meaning that the immune response was skewed towards a Th2 phenotype. There were no differences observed in lung CFU. These data demonstrate that Tregs in mycoplasma respiratory disease play a role in inflammation and disease severity, but have no effect on bacterial clearance. Importantly, depletion of Tregs causes a Th2-directed shift in the immune response.
Additional studies demonstrated that Tregs from mycoplasma-infected mice secreted IFN-γ or IL-17. IFN-γ + and IL-17+ Treg populations both preferentially expanded in response to M. pulmonis infection. Depletion of Tregs resulted in decreased secretion of IFN-γ and IL-17 by CD4+ non-Treg cells. Cocultures of Tregs and T helper cells from mycoplasmainfected mice secreted large amounts of IFN-γ and IL-17 when stimulated with mycoplasma membrane antigen. Levels of IL-4, IL-10, and IL-13 did not significantly increase in response to antigen. Together these studies demonstrate that mycoplasma respiratory disease is influenced by Tregs. These data further suggest that mycoplasma-specific Tregs include two unique subpopulations that express either IFN-γ or IL-17, and that these Tregs may promote the secretion of IFN-γ and IL-17 by T helper cells. This may represent a novel mechanism of Tregmediated immune suppression. This knowledge can assist in the development of treatments for mycoplasma respiratory disease and in the development of Treg-mediated therapies for a number of diseases.
Odeh, A. N.
"The Role of Regulatory T Cells in Mycoplasma Respiratory Infection" Fort Worth, Tx: University of North Texas Health Science Center;