Analysis of naïve lung CD4 T cells provides evidence of functional lung to lymph node migration.

The proportion of CD4 T cells with phenotypic and functional properties of naïve cells out of total CD4 T cells is similar in the lung parenchyma and lymph nodes. On treatment with a sphingosine-1-phosphate agonist, the frequency of these cells falls precipitously, but with a delay of ∼14 h compared with blood CD4 T cells; neither anti-CD62L nor pertussis toxin prevents entry of naïve CD4 T cells into the lung. Based on treatment with anti-CD62L and the use of CCR7(-/-) cells, lung naïve CD4 T cells appear to migrate to the mediastinal lymph nodes along a CD62L-independent, CCR7-dependent pathway. Cells that have entered the node in this manner are competent to respond to antigen. Thus, a portion (approximately one-half) of naïve CD4 T cells appears to enter the mediastinal lymph nodes through a blood-to-lung-to-lymph node route.