Expression and role of VLA-1 in resident memory CD8 T cell responses to respiratory mucosal viral-vectored immunization against tuberculosis.

Lung resident memory T cells (T) characterized by selective expression of mucosal integrins VLA-1 (α1β1) and CD103 (αβ7) are generated following primary respiratory viral infections. Despite recent progress, the generation of lung T and the role of mucosal integrins following viral vector respiratory mucosal immunization still remains poorly understood. Here by using a replication-defective viral vector tuberculosis vaccine, we show that lung Ag-specific CD8 T cells express both VLA-1 and CD103 following respiratory mucosal immunization. However, VLA-1 and CD103 are acquired in differential tissue sites with the former acquired during T cell priming in the draining lymph nodes and the latter acquired after T cells entered the lung. Once in the lung, Ag-specific CD8 T cells continue to express VLA-1 at high levels through the effector/expansion, contraction, and memory phases of T cell responses. Using a functional VLA-1 blocking mAb, we show that VLA-1 is not required for trafficking of these cells to the lung, but it negatively regulates them in the contraction phase. Furthermore, VLA-1 plays a negligible role in the maintenance of these cells in the lung. Our study provides new information on vaccine-inducible lung T and shall help develop effective viral vector respiratory mucosal tuberculosis vaccination strategies.