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The demonstration by Upham et al 1that human alveolar macrophages selectively inhibit proliferation of T cells by secretion of unidentified effector molecules raises the question as to whether pathological processes in the lung characterised by extensive macrophage recruitment or activation can have a systemic effect on T cell development.
It has been shown in several studies that patients with pulmonary tuberculosis who are not infected by HIV often show a lymphopenia principally affecting the CD4+ T cells.2 ,3 This appears to be a transient phenomenon as the CD4+ count reverts to normal after successful therapy.3 A similar transient CD4+ lymphopenia has also been observed after antigenic bronchial provocation in asthmatic subjects.4
It would be of great interest to determine whether this systemic phenomenon is due to the same mechanism as the one described by Uphamet al, whether it accounts (at least in part) for the so-called “idiopathic CD4+ T lymphopenia syndrome”,3and whether it affects the balance between Th1 and Th2 cells which may be critical to the pathogenesis of both asthma and tuberculosis.
authors’ reply Studies in a variety of species1-1-1-3 indicate that a substantial proportion of the recirculating T cell population is sequestered for significant periods during transit through the lung vascular bed, and many of these cells extravasate and move into the lung interstitium. The initial trapping of T cells in transit is due, at least in part, to local endothelial expression of inflammation associated molecules such as ICAM-1. This process is partially selective for recently activated T cells, and T lymphoblasts generated at immunoinflammatory foci distal to the lung readily enter the lung and therefore contribute to the local immunological milieu.1-3 1-4 Moreover, the extremely large size of this peripheral lung T cell population indicates that this is a physiological process which operates continuously in normal individuals,1–3 and it is conceivable (in our view highly likely) that it is further amplified in immunoinflammatory diseases in which high numbers of activated T cells are present in the circulation.1-4
As inferred by Dr Grange, these T cells are subjected to the powerful downregulatory influence of lung macrophages during their transit through lung tissue, resulting in a variety of functional changes including loss of proliferation capacity.1-1 1-3 1-5 While the precise mechanisms employed by the macrophages to modulate T cells are incompletely understood, it is clear that their overall efficiency in this regard is a reflection of their maturation/activation status.1-6 The suggestion that amplification of this process during inflammatory diseases characterised by enhanced lung macrophage recruitment/activation may result in significant effects on the overall recirculating T cell compartment is thus worthy of more detailed investigation.
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