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Am J Respir Crit Care Med. 2010 Apr 15;181(8):862-72. doi: 10.1164/rccm.200910-1583OC. Epub 2009 Dec 17.

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 information

  • 1Centre for Gene Therapeutics, M. G. DeGroote Institute for Infectious Disease Research, Hamilton, Ontario L8N 3Z5, Canada.

Abstract

RATIONALE:

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.

OBJECTIVES:

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.

MEASUREMENTS AND MAIN 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.

PMID:
20019338
[PubMed - indexed for MEDLINE]
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