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A rabbit model for mucosal immunity in the bowel. II. Local cellular reactivity to virus infection
1Department of Microbiology, University of Otago, Dunedin, New Zealand.
Insights
A rabbit model revealed that virus infection of the bowel triggers a localized immune response in gut-associated lymphoid tissues. This T-cell mediated immunity was sustained within the bowel wall, not systemically.
Area of Science:
- Immunology
- Gastroenterology
- Virology
Background:
- Understanding local immune responses in the gastrointestinal tract is crucial for addressing mucosal infections.
- Previous studies have limitations in assessing cellular reactivity within the bowel mucosa.
Purpose of the Study:
- To investigate local and systemic cellular immune responses to viral infection in the rabbit bowel mucosa.
- To characterize the kinetics and location of T-cell mediated immunity following parainfluenzavirus type 3 infection.
Main Methods:
- Adaptation of techniques for isolating viable lymphocytes from rabbit ileal mucosa.
- Infection of chronically isolated ileal loops in rabbits with parainfluenzavirus type 3 (PI-3).
- In vitro lympho-proliferation assays using isolates from local and systemic lymphoid tissues.
Main Results:
- Lamina propria lymphocytes (LPL) showed strong responses to mitogens, while intra-epithelial lymphocytes (IEL) responded poorly.
- A localized T-cell mediated immune response to PI-3 was detected in loop-associated lymphoid tissues (Peyer's patches, mesenteric lymph nodes, lamina propriae).
- Immune response was highest in Peyer's patches early post-infection, sustained longer in mesenteric lymph nodes and lamina propriae, with no systemic reactivity observed.
Conclusions:
- The study demonstrates a highly localized T-cell mediated immune response within the bowel wall following viral infection.
- Intra-epithelial lymphocytes appear anergic in this model.
- Immunity is sustained in gut-associated lymphoid tissues and the bowel wall itself, highlighting compartmentalized mucosal immunity.
Abstract:
An animal model was used to examine local and systemic cellular reactivity against virus infection of bowel mucosa. Firstly, existing techniques for extracting lymphoid cells from the dispersed populations of the bowel mucosa were adapted for use in rabbits and viable lymphocytes were isolated from the lapine ileal mucosa in numbers suitable for assay. Lamina propria lymphocytes (LPL) showed a strong blastogenic response to T-cell mitogens but intra-epithelial lymphocytes (IEL) responded poorly, even in the presence of splenic accessory cells. Next, chronically isolated ileal loops in rabbits were infected with parainfluenzavirus type 3 (PI-3) and isolates from the organized and dispersed lymphoid tissues associated with infected ileal mucosae and those from systemic lymphoid sites were used in in vitro assays of virus-specific lympho-proliferation. A T-cell-mediated immune response against PI-3 was mounted in lymphoid tissues associated with the infected loops, appearing first in loop Peyer's patches (PP) at Day 4 and in mesenteric lymph nodes (MLN) and lamina propriae at Day 7 after infection. The response in PP had waned by 21 days but was sustained in the other sites for at least 42 days. Epithelial lymphocytes were consistently anergic and there was no evidence of specific reactivity at systemic lymphoid sites or elsewhere in the bowel. Thus, a highly localized T-cell-mediated response was sustained, not only in organized lymphoid tissues but also in the bowel wall itself, following infection with a novel antigen.