Article

Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas.

Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Immunity (impact factor: 21.64). 05/2011; 34(5):807-19. DOI:10.1016/j.immuni.2011.03.022 pp.807-19
Source: PubMed

ABSTRACT Cell-mediated adaptive immunity is critical for host defense, but little is known about T cell behavior during delivery of effector function. Here we investigate relationships among antigen presentation, T cell motility, and local production of effector cytokines by CD4+ T cells within hepatic granulomas triggered by Bacille Calmette-Guérin or Mycobacterium tuberculosis. At steady-state, only small fractions of mycobacteria-specific T cells showed antigen-induced migration arrest within granulomas, resulting in low-level, polarized secretion of cytokines. However, exogenous antigen elicited rapid arrest and robust cytokine production by the vast majority of effector T cells. These findings suggest that limited antigen presentation and/or recognition within granulomas evoke a muted T cell response drawing on only a fraction of the host's potential effector capacity. Our results provide new insights into the regulation of host-protective functions, especially how antigen availability influences T cell dynamics and, in turn, effector T cell function during chronic infection.

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Keywords

antigen availability influences T cell dynamics
 
antigen-induced migration arrest
 
Bacille Calmette-Guérin
 
CD4+ T cells
 
Cell-mediated adaptive immunity
 
chronic infection
 
effector T cell function
 
effector T cells
 
exogenous antigen elicited rapid arrest
 
granulomas evoke
 
hepatic granulomas
 
host's potential effector capacity
 
host-protective functions
 
limited antigen presentation
 
mycobacteria-specific T cells
 
robust cytokine production
 
small fractions
 
T cell behavior
 
T cell motility
 
vast majority