Lung CD4 Tissue-Resident Memory T Cells Mediate Adaptive Immunity Induced by Previous Infection of Mice with .

Th1 and Th17 cells have an established role in protective immunity to , but this evidence is based largely on peripheral T cells. There is emerging evidence that local tissue-resident memory T (T) cells that accumulate in tissue following mucosal infection may be crucial for long-term immunity. In this study, we examined the role of respiratory CD4 T cells in immunity to Natural immunity to induced by infection is considered long lasting and effective at preventing reinfection. Consistent with this, we found that convalescent mice rapidly cleared the bacteria after reinfection. Furthermore, CD4 T cells with a T cell phenotype (CD44CD62LCD69 or CD44CD62LCD69CD103) accumulated in the lungs of mice during infection with and significantly expanded through local proliferation following reinfection. These CD4 T cells were specific and secreted IL-17 or IL-17 and IFN-γ. Treatment of mice with FTY720, which prevented migration of T and B cells from lymph nodes to the circulation, significantly exacerbated infection. This was associated with significantly reduced infiltration of central memory T cells and B cells into the lungs. However, the local expansion of T cells and the associated rapid clearance of the secondary infection were not affected by treatment with FTY720 before rechallenge. Moreover, adoptive transfer of lung CD4 T cells conferred protection in naive mice. Our findings reveal that Ag-specific CD4 T cells play a critical role in adaptive immunity against reinfection and memory induced by natural infection with .