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.
BACKGROUND
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.


OBJECTIVE
Using a model of adenovirus-based intranasal immunization we investigated the immune property and the mechanisms of maintenance of airway luminal CD8 T cells.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jeyanathan
Mangalakumari
M
Centre for Gene Therapeutics, M. G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario L8N 3Z5, Canada.
Mu
Jingyu
J
McCormick
Sarah
S
Damjanovic
Daniela
D
Small
Cherrie-Lee
CL
Shaler
Christopher R
CR
Kugathasan
Kapilan
K
Xing
Zhou
Z
D000281:Administration, Intranasal; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000942:Antigens, Bacterial / Q000187:drug effects / Q000276:immunology; D001980:Bronchi / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000517:prevention & control*
D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; C072681:Mycobacterium tuberculosis antigens