Mucosal surfaces are a significant portal of entry for many pathogens. An elaborate immune system, consisting of lymphocytes contained within distinct regions or dispersed throughout the epithelium, exists at mucosal surfaces to deal with mucosal pathogens. By many criteria, the mucosal immune response can be considered to operate in a somewhat independent manner from systemic immune responses. Disparate mucosal lymphoid compartments have also been proposed to be """"""""linked"""""""" by recirculating lymphocyte populations to form """"""""the common mucosal immune system"""""""". Thus, immunization at one mucosal site can result in the dissemination of specific-immunocytes to distal mucosal surfaces. Although a number of studies examined the nature of the immune response to particular mucosal pathogens, many of these organisms are able to colonize and stimulate specific immunity at only one mucosal site. Thus, it has been difficult to study potential cross-priming between mucosal sites using the same pathogen. In this application we will focus on mucosal T cell immunity at the oral cavity. We Will utilize reovirus 1/L infection after various routes of immunization to study oral mucosal immunity in the wider context of the common mucosal immune system. We have demonstrated reovirus-specific immunity in the murine tonsil equivalent (Nasal Associated Lymphoid Tissue), salivary glands, and associated lymph nodes. Because reovirus 1/L is an effective gut-mucosal immunogen, as well as a respiratory pathogen, this virus is an excellent candidate for our studies. In particular, we propose to investigate the following five specific aims. 1) Analysis of salivary gland and oral lymphoid T cell responses to reovirus infection. 2) Analysis of mucosal cytokine responses to reovirus infection. 3) Definition of specific CTL and TH epitopes of reovirus within distinct mucosal sites. 4) Functional analysis of epitope-specific T cell populations in murine models for infection/protection studies. 5) Analysis of the mechanism of action of CTLs generated at mucosal surfaces. Studies aimed at understanding the nature of mucosal immune responses and the development of methods for effective mucosal immunization are important for practical, as well as theoretical reasons since effective mucosal immunity is likely important for the control and resolution of infections which commence at mucosal surfaces.
| Bharhani, Mantej S; Grewal, Jasvir S; Peppler, Richard et al. (2007) Comprehensive phenotypic analysis of the gut intra-epithelial lymphocyte compartment: perturbations induced by acute reovirus 1/L infection of the gastrointestinal tract. Int Immunol 19:567-79 |
| Bharhani, Mantej S; Grewal, Jasvir S; Pilgrim, Mark J et al. (2005) Reovirus serotype 1/strain Lang-stimulated activation of antigen-specific T lymphocytes in Peyer's patches and distal gut-mucosal sites: activation status and cytotoxic mechanisms. J Immunol 174:3580-9 |
| Thompson, A H; McRoberts, J G; Crowe, S R et al. (1999) Optimal induction of upper respiratory tract immunity to reovirus 1/L by combined upper and lower respiratory tract inoculation. Vaccine 17:1404-15 |
| Thompson, A H; London, L; London, S D (1999) Heterogeneous cytokine production by acutely stimulated bronchoalveolar T lymphocytes in reovirus 1/Lang-infected mice. Cell Immunol 198:120-30 |
