White blood cells called T cells roam our bodies, moving from one lymph node to another looking for foreign invaders to fight. Francis Crick Institute scientists have now discovered a new biochemical pathway that controls how T cells move between and adhere to lymph nodes.
Victor Tybulewicz of the Crick and Imperial College London led the work. He explained: "T lymphocytes, or T cells, are a critical part of the immune system. They have a protein on their surface called the T cell antigen receptor (TCR), which enables them to detect and pathogens, such as viruses and bacteria, and mount an immune response to eliminate the infection. In order to fight many different infections, humans have T cells with millions of different TCRs. Each T cell only makes one type of TCR, specific for one infection.
"Most T cells in the body reside in special lymphoid organs such as lymph nodes or the spleen. Typically, T cells spend several hours in one lymph node before moving on to another through the blood, patrolling the body and looking for signs of infection.
"If they stayed resident in just one lymph node, they might not detect the infection that their TCR is specific for. For example, a T cell with a TCR specific for the flu virus would not be able to detect flu unless it passes through a lymph node next to the lungs, where it can recognise signs of flu infection and mount an immune response."
To find out more about T cell migration, the research team used mouse genetics, biochemistry and imaging, including intra-vital imaging, which allowed them to see the T cells migrating inside a lymph node inside a living animal.
The team found that an enzyme called WNK1 plays important roles in how T cells both migrate to lymph nodes and adhere to other cells. WNK1, which has previously only been studied in the kidneys, controls T cell migration in part by controlling the movement of salt ions across the cell membrane. Its role in the kidneys is to regulate the uptake of salt from urine back into the blood system.
The scientists speculate that in T cells, the movement of salt ions could be localised to different parts of the cell. The forward leading edge of the cell could take up the salt ions and cause the front of the cell to swell as water comes in after the salt. In contrast at the rear of the cell (the trailing edge), the salt ions may be pumped out and cause the cell to shrink at the rear, causing forward movement.
WNK1's role in T cell adhesion is carried out through a separate process, where the enzyme turns off the adhesion pathway. The scientists speculate that this dual role for WNK1 may serve to balance migration and adhesion processes in T cells.
Dr Tybulewicz said: "This work suggests that movement of salt ions across the cell membrane may be important for the movement of T cells. This was highly unexpected and has opened up a new avenue of research that we and others are now likely to follow up.
"Pathways that control the migration of T cells around the body could be targets of drugs that modify immune responses."
The paper, WNK1 kinase balances T cell adhesion versus migration in vivo, is published in Nature Immunology.