Investigation into the mechanisms of T cell homing to the lung in health and disease

Human T lymphocytes do not circulate around the body in a random fashion. Expression of certain receptors ensure that they are guided around the body to maximise the efficiency of the immune system in combating infection, a process known as lymphocyte homing. In some disease processes there may be an over exuberant immune response effected in part by unnecessary lymphocyte homing. Mechanisms of lymphocyte homing to the lung are far from clear. Analysis of the chemokine and activation marker expression of T cells derived from human lung resection specimens, bronchoalveolar lavage fluid and peripheral blood in both health and disease by flow cytometry, may help to define patterns of expression which may be specific to the presence of a T cells within the lung or specific to a particular disease process. Using these techniques, I have demonstrated that there is polarization of the chemokine receptors CCR3 and CCR4 on bronchoalveolar Th2 cells in both health and disease, thus providing a potential mechanism for their differential recruitment to the lung in allergic disease such as asthma. I have provided evidence for the existence of a resident lung T cell population characterised by expression of multiple activation markers, and have shown that a high percentage of these cells express CXCR6 suggesting that this receptor may have a role in the recruitment and/or retention of these cells within the lung. Finally, I have demonstrated that in sarcoidosis, a disease where there is abnormal T cell accumulation within the lung, more BAL T cells express CXCR6 compared to cells derived from asthmatic patients or healthy controls, again suggesting a potential role for this receptor in T cell homing to the human lung in both health and disease.