Persistence in Temporary Lung Niches: A Survival Strategy of Lung-Resident Memory CD8(+) T Cells

Takamura, Shiki

It is currently unclear what signals are responsible for the upregulation of VLA-1 on CD8 + T cells. Antigen-specific CD8 + T cells in nonlymphoid tissues are mostly VLA-1 + , indicating the universal role of this integrin in the retention of cells that are ''basally'' recruited to the nonlymphoid tissues (103) . Interestingly, large numbers of VLA-1 + CD8 + T cells accumulate in the lung following respiratory, but not systemic infections/vaccinations (108, 123) . Furthermore, local inflammation in the presence of cognate antigen, but not inflammation alone, enables the conversion of circulating CD8 + T cells into VLA-1 + CD8 + T RM cells in the lung (123) , suggesting the impact of local reactivation on the upregulation or maintenance of VLA-1 expression on actively recruited CD8 + T cells to the inflamed nonlymphoid tissues. In support of this, CD49a expression defines a marker of CD8 + T RM cells having a highly cytolytic potential (13) . However, additional experiments are required to precisely resolve the question where and when upregulation of VLA-1 occurs. On the other hand, transforming growth factor-b (TGF-b) signaling is known to be necessary for the upregulation of integrin aEb7 as lack of this signal results in the complete loss of CD103 + CD8 + T cells in the lung (51, 133) . CD4 + T cell-derived interferon-c (IFN-c) potentially contributes to the secretion of TGF-b in the lung, thereby helping CD8 + T cell retention in the airways by inducing the expression of CD103 (70) . Based on these data, the upregulation of integrins in the lung and the consequential regulation of tissue distribution of the effector T cells could also be considered a consequence of local tissuederived instruction that promotes T RM differentiation.