SELECTIVE-INHIBITION OF T-CELL PROLIFERATION BUT NOT EXPRESSION OF EFFECTOR FUNCTION BY HUMAN ALVEOLAR MACROPHAGES

Background - Alveolar macrophages are thought to play an important par t in regulating lung immune responses. While it is clear that human al veolar macrophages suppress T cell proliferation in vitro, the mechani sms by which this is achieved are not clear, nor is it known whether a lveolar macrophages also inhibit other aspects of T cell function. Met hods - Peripheral blood mononuclear cells were stimulated with phytoha emagglutinin or house dust mite allergen, and cultured with variable n umbers of autologous alveolar macrophages obtained by bronchoalveolar lavage from 20 normal subjects. Results - Alveolar macrophages induced a reversible inhibition of T cell proliferation in response to both m itogen and allergen stimulation, with the latter being considerably mo re susceptible to inhibition. This was achieved via heterogenous mecha nisms, involving both soluble factors derived from alveolar macrophage s and cell-cell contact. Despite inhibiting proliferation, alveolar ma crophages had little or no effect on T cell calcium flux, the characte ristic changes in CD3, CD2, CD28 and interleukin-2 (IL2) receptor expr ession which accompany normal T cell activation, and IL-2 and interfer on gamma secretion. In contrast, alveolar macrophages inhibited the ty rosine phosphorylation of proteins which may be involved in IL-2 recep tor-associated signal transduction. Conclusions - The immunoregulatory properties of alveolar macrophages are relatively selective, allowing T cell activation and cytokine secretion while inhibiting T cell prol iferation within the lung.