The purpose of these studies was to define the contributions of T helper 2 cells and dendritic cells toward the development of immunopathology during mycoplasma respiratory disease. IFN-γ+ CD8+ T cells, IFN-γ+ Th1 cells and IL-13+ Th2 cells developed over the course of mycoplasma infection. By day 14 post-infection, the results demonstrated a significant and preferential increase of an IL-13 + Th2 cell sub-population in the LRNs. Additional studies using STAT4 -/- animals, which have a Th2 polarized environment, demonstrated no difference in disease compared to the wild-type animals. Absence of STAT6, which strongly contributes to a Th1 polarized environment, conveyed significantly more protection from mycoplasma disease in immunized mice compared to STAT4 -/- and WT mice. By day 14 post-infection, all mice had significantly more IL-13+ Th2 cells than IFN-γ + Th1 in the LRN compared to STAT6-/- immunized mice, thus suggesting that the reduction in the IL-13+ Th2 population leads to protection, while an increase in Th2 is pathogenic.
Additional studies demonstrated that pulmonary dendritic cells support the mycoplasma-specific CD4+ and CD8+ T cell activation when stimulated with mycoplasma antigen. Knowing that T cells and DCs have an intimate relationship during mycoplasma disease, sub-classes of cytokine differentiated BMDCs were created to attempt to skew to the protective arm of immunity against mycoplasma disease. However, in vivo adoptive transfer studies demonstrated antigen pulsed DCs accelerated and exacerbated the pathological effects of mycoplasma disease. The exacerbation was antigen-specific and lymphocyte dependent. Mice that received antigen pulsed DCs demonstrated a significant increase in IL-13+ Th2 cell sub-population in the LRNs with a similar trend found in the lungs prior to infection. The same exacerbation was seen when antigen pulsed pulmonary DCs were adoptively transferred into mice, but not with antigen pulsed splenic DCs. Prior to infection, mice that received antigen-pulsed pulmonary DC, not splenic DC, had a significant increase in a IL-13+ Th2 population in the LRNs. Taken collectively, these studies demonstrate two key players in the development of the detrimental response against mycoplasma disease. This knowledge will assist in the development of targeted vaccines that will promote protection over pathology.
|Advisor:||Simecka, Jerry W.|
|Commitee:||Aschenbrenner, John, Berg, Rance E., Brown, Mary B., Mathew, Porunelloor|
|School:||University of North Texas Health Science Center at Fort Worth|
|Department:||Microbiology and Immunology|
|School Location:||United States -- Texas|
|Source:||DAI-B 71/08, Dissertation Abstracts International|
|Subjects:||Cellular biology, Microbiology, Immunology|
|Keywords:||Dendritic cells, Immunopathology, Lung immunology, Mycoplasma, T cells, Th1, Th2|
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