Dissertation Information for Allison T. TheileNAME:
DEGREE:
DISCIPLINE:
SCHOOL: ADVISORS: COMMITTEE MEMBERS: MPACT Status: Incomplete - Not_Inspected Title: Effects of viral infections on pulmonary immunity Abstract: Secondary bacterial infections are a common complication following viral infections. In addition, respiratory viral infections have been linked to the development of pulmonary disorders later in life. Dendritic cells (DCs) have been shown to be the primary initiators of the immune response in the lung due to their function as antigen presenting cells (APCs). Therefore we hypothesized that a viral infection of lung DCs results in a decrease in their APC ability creating a state of immunosuppression in the lung, which could lead to the development of further pulmonary disease. To address this question, we infected lung DCs both in vitro and in vivo with a replication deficient adenovirus (Ad) as a model of Ad infection. Ad-infected lung DCs had a decreased ability to stimulate T cell proliferation compared to uninfected controls. This impairment was not due to a decrease in the cell surface expression of MHC class I and II molecules or the costimulatory molecules CD80, CD86, CD40 and OX40L, or a lack of IL-2. Further studies showed that this suppression was not due to a soluble factor, but seemed to be contact-dependent. UV-irradiation of Ad prior to infection abrogated lung DC functional suppression, indicating that viral protein synthesis is required. Examination of T cells demonstrated that Ad-infected DCs were not inducing regulatory T cells. However, T cells reisolated from primary cocultures with Ad-infected DCs were able to proliferate in secondary culture in the presence of IL-2, suggesting that coculture with Ad-infected DCs may induce anergy in the T cells. |
MPACT Scores for Allison T. TheileA = 0 Advisors and Advisees Graph |