Abstract
Specific T cell responses are central for protection against infection with M. tuberculosis. Here we show that mycobacteria-specific CD4 and CD8 T cells accumulated in the lung but not in the mediastinal lymph node (MLN) at different time points after M. tuberculosis infection or BCG immunization. Proliferating specific T cells were found in the lung after infection and immunization. Pulmonary, but not MLN-derived CD4 and CD8 T cells, from M. tuberculosis-infected mice secreted IFN-γ after stimulation with different mycobacterial peptides. Mycobacteria-specific resident memory CD4 and CD8 T cells (TRM) expressing PD-1 accumulated in the lung after aerosol infection and intratracheal (i.t.) -but not subcutaneous (s.c.)- BCG immunization. Chemical inhibition of recirculation indicated that TRM were generated in the lung after BCG i.t. immunization. In summary, mycobacteria specific-TRM accumulate in the lung during i.t. but not s.c. immunization or M. tuberculosis infection. Collectively our data suggests that priming, accumulation and/or expansion of specific T cells during BCG immunization and M. tuberculosis infection occurs in the lung.
Highlights
Tuberculosis (TB) is the leading cause of infectious death; in 2018, 10 million people developed and 1.5 million patients died from TB [1]
CD4 and CD8 T cells were activated in the mediastinal lymph node (MLN) after infection with M. tuberculosis as measured by the expression of CD44 as compared to uninfected controls (Figure 1D)
We found that the i.t. immunization induced a higher number of mycobacterial Ag85B240−254 and TB10.44−11 tetramerbinding CD4 and CD8 T cells in the lung as compared to those immunized via the s.c. route (Figures 5A,B)
Summary
Tuberculosis (TB) is the leading cause of infectious death; in 2018, 10 million people developed and 1.5 million patients died from TB [1]. The risk of developing TB increases during HIV and Mycobacterium tuberculosis co-infection, suggesting that impairment of T cell-mediated immune responses reactivates the asymptomatic infection. The only TB vaccine, BCG (Bacille Calmette–Guérin) in use since 1921, offers substantial protection of infants against meningeal or miliary TB. Protection against pulmonary TB in adults is not sufficient. The BCG vaccine, to a large extent and with some exceptions, mitigates only the most severe aspects of infection and exhibits a highly variable efficacy, especially in high-burden areas [2]. Developing new and efficacious TB vaccines, a very effective intervention for containing the TB spread, is a critical unmet public health need [3]
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