[PDF][PDF] Intravital imaging reveals limited antigen presentation and T cell effector function in mycobacterial granulomas

JG Egen, AG Rothfuchs, CG Feng, MA Horwitz, A Sher… - Immunity, 2011 - cell.com
JG Egen, AG Rothfuchs, CG Feng, MA Horwitz, A Sher, RN Germain
Immunity, 2011cell.com
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 …
Summary
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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