Initiation of the adaptive immune response to <i>Mycobacterium tuberculosis</i> depends on antigen production in the local lymph node, not the lungs

TLDR

The adaptive immune response to Mycobacterium tuberculosis is markedly delayed relative to other infections, permitting extensive bacterial growth in the lungs during the preimmune phase. Using adoptive transfer of Ag85B‑specific CD4⁺ T cells, the study shows that this delay originates from a postponed initial activation of CD4⁺ T cells that first occurs in the mediastinal lymph node draining the lungs. The data reveal that early T‑cell activation depends on antigen produced by bacteria within the lymph node—despite the lungs harboring 100‑fold more bacteria—and that dendritic‑cell transport from the lungs does not hasten activation, indicating that the delay is due to bacteria residing in a compartment that cannot be mobilized to the lymph node.

Abstract

The onset of the adaptive immune response to Mycobacterium tuberculosis is delayed compared with that of other infections or immunization, and allows the bacterial population in the lungs to expand markedly during the preimmune phase of infection. We used adoptive transfer of M. tuberculosis Ag85B-specific CD4+ T cells to determine that the delayed adaptive response is caused by a delay in initial activation of CD4+ T cells, which occurs earliest in the local lung-draining mediastinal lymph node. We also found that initial activation of Ag85B-specific T cells depends on production of antigen by bacteria in the lymph node, despite the presence of 100-fold more bacteria in the lungs. Although dendritic cells have been found to transport M. tuberculosis from the lungs to the local lymph node, airway administration of LPS did not accelerate transport of bacteria to the lymph node and did not accelerate activation of Ag85B-specific T cells. These results indicate that delayed initial activation of CD4+ T cells in tuberculosis is caused by the presence of the bacteria in a compartment that cannot be mobilized from the lungs to the lymph node, where initial T cell activation occurs.