Control of Lymphocyte Trafﬁcking Through the Lung
In general, lymphocytes are not sessile cells but travel throughout the body continuously using the blood and lymph as routes connecting lymphoid and nonlymphoid organs (1). At any given time point there are only about 2% of all lymphoid cells of the body in the blood (2) and the composition of lymphocytes in the organs di¡ers greatly (3).Thus, a blood sample will only be representative of the situation in the lung, e.g., in asthma, if the alteration in numbers, subset composition, and activation in the bronchial wall is mirrored in qualitative and quantitative aspects in the blood (4).Minor changes in the rate of tra⁄cking of lymphocytes to a speci¢c area of the lung can eventually result in an impressive local accumulation without obvious e¡ects on lymphocyte numbers in the blood. Before alterations of lymphocyte subsets in asthma can be interpreted meaningfully, the compartmentalization of lymphocyte subsets in the healthy lung has to be de¢ned. In addition, not only the rate of entry into the lung but also the local proliferation, cell death, and, ¢nally, the exit from the lung to the draining lymph nodes must be determined (5). In a recent review, immune dysregulation was suggested as a cause for allergic asthma, e.g.,Th1 toTh2 reactions (6), but it remains tobe shownwhether speci¢c subsets of lymphocytes are recruited or the cells enter at random but di¡erentiate at a di¡erent tempo.The role of di¡erent regulatory factors, such as adhesion molecules, will be discussed using typical examples, and the major ¢elds of future research in the dynamic situation and potential therapeutic implications will be outlined.