Intravital Imaging Reveals Limited Antigen Presentation and T Cell Effector Function in Mycobacterial Granulomas

SummaryCell-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.

► Effector T cells within mycobacterial granulomas show limited antigen activation
► Effector T cells within granulomas have submaximal responses
► Low frequency of arrested effector T cells display polarized cytokine secretion
► Effector T cell motility and cytokine production have an inverse relationship