15 August 2005: Exit pass for T lymphocytes
The passage of immune cells throughout the body is more tightly regulated than previously thought, report two independent research groups.
Lymphocytes, a group of white blood cell that control the distribution and activity of other immune cells, are known to migrate from the blood into lymphoid and peripheral tissues under highly ordered, complex events involving numerous different molecules. But the exit of lymphocytes from peripheral tissue, such as skin, was thought to be random.
Now, researchers in the US and Europe have shown that the process is not random at all. They found that T lymphocytes in lymph fluid expressed a chemokine receptor called CCR7, while T lymphocytes in peripheral tissues did not express the receptor.
The team, led by Eugene Butcher at the Stanford University School of Medicine, looked at mice that lacked the CCR7 receptor altogether. Lymphocytes in these mice stayed in the tissues and never exited into the lymphatic vessels, supporting the hypothesis that CCR7 is needed for exit from peripheral tissues.
'Exit is likely to be as important as entry in controlling the accumulation of lymphocytes at peripheral sites,' write Butcher and colleagues. The importance of CCR7 in lymphocyte transit may also help to explain unpublished observations of lymphocyte accumulation in the gastrointestinal tract, lung and body cavities of mouse mutants lacking the gene for CCR7, they added.
While Butcher and colleagues were making these discoveries, a separate team led by Andrew Luster at the Massachusetts General Hospital, Harvard Medical School, found that CCR7 was essential for lymphocyte exit from the lungs in a mouse model of asthma.
Butcher's team proposes that expression of tissue-specific or inflammatory chemokine receptors together might determine whether CCR7+ T lymphocytes stay in the lymphatic system or enter peripheral tissues. Once in the peripheral tissues, they suggest, a balance in expression of chemokine receptors and CCR7 might determine where CCR7+ T lymphocytes migrate to next.
Both groups' findings have implications for pharmaceutical intervention in the future. 'An imbalance in these migration signals might cause the accumulation of CCR7+ effector T cells in the peripheral tissues found in inflammatory and autoimmune disease,' write Luster and colleagues in a report of their work. Bea Perks
G F Debes et al, Nat. Immunol., 2005, (DOI: 10.1038/ni1238
S K Bromley, S Y Thomas and A D Luster, Nat. Immunol., 2005, (DOI: 10.1038/ni1240)