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

Takamura, Shiki

CCR9 for the intestines, and cutaneous lymphocyteassociated antigen [CLA], CCR4, and CCR10 for the skin, respectively), molecules that specifically regulate T cell trafficking to the lung have not yet been reported. Instead, general factors such as lymphocyte function-associated antigen-1 (LFA-1) (125) and inflammatory chemokine receptors CCR5 and CXC chemokine receptor 3 (CXCR3) have been shown to be involved (134) . CCR5 ligands are constitutively expressed in the normal lung and regulate the basal recruitment of CCR5 + effector CD8 + T cells to the interstitium (33) . Upon respiratory virus infection, the expression of CCR5 binding chemokines as well as CXCR3 binding chemokines is upregulated in the lung (64, 134) , and various cell types are involved in the secretion of these chemokines, including epithelial cells, DCs, macrophages, endothelial cells, and mast cells (22, 99, 124) . CCR5 is also transiently expressed on the surface of antigen-experienced CD8 + T cells in the circulation shortly after respiratory virus infection (peaking at day 2 postinfection), and this upregulation is probably induced by proinflammatory cytokines (64) . Since only limited numbers of virally primed antigen-specific CD8 + T cells exist at this time point, CCR5-mediated active recruitment of cells to the lung airways is antigen independent (23). This influx (3-5 days) is a part of acute response during respiratory virus infections (44) , and antigen-nonspecific memory CD8 + T cells recruited to the lung airways provide ''innate'' protection (64) . Nevertheless, the lack of CCR5 alone has essentially no impact on the active recruitment of expanded antigen-specific effector CD8 + T cells to the lung (5-10 days) (30, 66) , suggesting the redundancy of signals through various inflammatory chemokine receptors in this process.