Date of Award

2006

Document Type

Thesis

Department

Microbiology and Immunology

College

College of Graduate Studies

First Advisor

Steven O. London

Second Advisor

Edward Balish

Third Advisor

Laura M. Kasman

Fourth Advisor

Lucille London

Fifth Advisor

Natalie Sutkowski

Abstract

The salivary gland is the predominant effector site of mucosal immune responses in the oral cavity. In mice, the salivary glands are known to receive immune lymphocytes stimulated in inductive sites such as the gut- and nasal-associated lymphoid tissues, thus, allowing the production of antigen-specific antibodies in saliva. However, the potential of the salivary gland as a mucosal inductive site has not been fully explored. In order to investigate this concept, we have developed a model resulting in a focused salivary gland infection using intraglandular delivery of tissue culture-derived murine cytomegalovirus (tcMCMV). Utilizing this route of infection, we were capable of inducing a mucosal immune response to MCMV while limiting systemic pathology resulting from the virus. This infection protocol allowed us to study the consequences of initiating an immune response in the salivary gland. In order to determine whether the route of infection influenced the cell surface phenotype of cells infiltrating the salivary gland, mice were infected with MCMV via two different routes, a focused salivary gland infection (IG tcMCMV) or a systemic infection (IP MCMV). Over a two-week time course, animals were sacrificed and systemic and mucosal tissues were harvested for flow cytomeric analysis. Our studies were focused on the analysis of the NK, T, and B cell responses in the salivary gland as well as the acquisition of specific homing receptors on the infiltrating cells in the salivary gland after either mucosal or systemic infection. Our results demonstrated that there was an overall increase in the total number of lymphocytes obtained from the salivary gland, as well as the salivary gland associated lymph nodes, following either mucosal or systemic infection with MCMV. The absolute number of NK cells, and to a lesser extent NKT cells, in the salivary gland were increased after infection. Additionally, an increase in the absolute number of both T and B cells in the salivary gland and salivary gland associated lymph nodes was also observed. As well as analyzing the traditional cell surface phenotypes of the infiltrating cells, we also determined the pattern of homing receptor expression. We chose to focus our initial studies on the expression of α4β 1, α4β7, and L-selectin. α4β 1 is a mucosal homing receptor known to be associated with the tonsils. α4β7 is a gut-associated mucosal homing receptor. L-selection is a systemic homing receptor expressed in the peripheral lymph nodes. We demonstrated that α4β1 and a α4β7 expression is increased in the salivary gland but not the salivary gland associated lymph nodes, spleen, or peripheral lymph nodes following MCMV infection. However, L-selectin was mainly expressed in the spleen and both the peripheral and salivary gland associated lymph nodes after MCMV infection. Therefore, the expression of both α4β1 and α4β7 homing receptors in the salivary gland following MCMV infection could possibly be used to define lymphocytes that preferentially home to the salivary gland.

Rights

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