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

Takamura, Shiki

In addition to late antigen recognition, local cytokine signaling is also crucial for the formation of CD8 + T RM cells in the lung. TGF-b is produced by a wide variety of cell types in the lung, including alveolar macrophages, neutrophils, activated alveolar epithelial cells and endothelial cells (31) . Although TGF-b is known as a profibrotic cytokine and its overproduction is critically associated with pulmonary fibrosis (31), influenza virus-infected animals recover without the acquisition of lung fibrosis (68, 123) , suggesting that TGFb production as well as its activation is rather stable during the course of infection. This is true despite the fact that some strains of influenza virus surface protein can activate latent TGF-b in the lung (109) . Local TGF-b signaling does not require Sma-and Mad-related protein 4 (Smad4) (51) , and plays a key role in the downregulation of T-box transcription factors Eomes and T-bet in effector CD8 + T cells, both of which are required for effector to T RM transition (82) . Upon skin CD8 + T RM differentiation, Eomes expression is fully extinguished, while T-box expression remains at a low level, which sustains CD122 expression (IL-15 receptor b-chain) and enables to receive IL-15-medaited survival signal (82) .