1. Murine Airway Luminal Antituberculosis Memory CD8 T Cells by Mucosal Immunization Are Maintained Via Antigen-Driven In Situ Proliferation, Independent of Peripheral T Cell Recruitment
- Author
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Cherrie-Lee Small, Daniela Damjanovic, Mangalakumari Jeyanathan, Christopher R. Shaler, Jingyu Mu, Sarah McCormick, Kapilan Kugathasan, and Zhou Xing
- Subjects
Pulmonary and Respiratory Medicine ,T cell ,Lymphocyte ,Immunization, Secondary ,Bronchi ,Respiratory Mucosa ,CD8-Positive T-Lymphocytes ,Critical Care and Intensive Care Medicine ,Mice ,Interleukin 21 ,Immune system ,Antigen ,medicine ,Animals ,Cytotoxic T cell ,Tuberculosis Vaccines ,Lung ,Tuberculosis, Pulmonary ,Administration, Intranasal ,Cell Proliferation ,Antigens, Bacterial ,Mice, Inbred BALB C ,business.industry ,T lymphocyte ,respiratory system ,Adoptive Transfer ,Disease Models, Animal ,medicine.anatomical_structure ,Immunology ,Female ,business ,Immunologic Memory ,CD8 - Abstract
The airway luminal memory CD8 T cells induced by respiratory mucosal immunization in a murine model have been found to be critical to antituberculosis immunity. However, the mechanisms of their maintenance on airway mucosal surface still remain poorly understood.Using a model of adenovirus-based intranasal immunization we investigated the immune property and the mechanisms of maintenance of airway luminal CD8 T cells.Immune properties of airway luminal Mycobacterium tuberculosis antigen-specific CD8 T cells were examined. Proliferation of airway luminal CD8 T cells was determined by in vivo T cell-labeling techniques. The role of peripheral T cell recruitment in maintaining airway luminal CD8 T cells was investigated by blocking lymphocyte trafficking from lymphoid and peripheral tissues. The requirement of M. tuberculosis antigens for in situ T cell proliferation was evaluated using a T cell transfer approach. An airway M. tuberculosis challenge model was used to study the relationship between CD8 T cell-mediated protection and peripheral T cell recruitment.Intranasal immunization leads to elicitation of persisting M. tuberculosis antigen-specific CD8 T cells in the airway lumen, which display an activated effector memory phenotype different from those in peripheral tissues. Airway luminal T cells continuously proliferate in an antigen-dependent manner, and can be maintained even in the absence of peripheral T cell recruitment. The lungs equipped with such CD8 T cells are protected from airway M. tuberculosis challenge independent of both peripheral T cell supply and CD4 T cells.Vaccine-inducible airway luminal antituberculosis memory CD8 T cells are self-renewable in an antigen-dependent manner, and can be maintained independent of peripheral T cell supply.
- Published
- 2010