Suppression of T-cell activation by pulmonary alveolar macrophages: dissociation of effects on TcR, IL-2R expression, and proliferation

Suppression of local T-cell activation in the lower respiratory tract by resident pulmonary alveolar macrophages (PAMs) is believed to play an important role in the maintenance of local immunological homeostasis. However, the mechanism(s) by which pulmonary alveolar macrophages regulate T-cell responses are poorly characterized. The present study examines early events during the activation process in mitogen-stimulated T-cell cultures, in which proliferation was completely blocked by the presence of pulmonary alveolar macrophages. Despite inhibition of proliferation, the T-cells demonstrated normal Ca++ flux, normal modulation of surface expression of CD3 and T-cell receptor alpha/beta (TCR alpha/beta), upregulation of interleukin-2 receptors alpha and beta (IL-2R alpha and IL-2R beta), and secretion of high levels of interleukin-2 (IL-2). Thus, pulmonary alveolar macrophage regulation of T-cell activation appears to permit initial expression of effector function, but selectively inhibits further amplification of the overall T-cell response by limiting clonal expansion of the activated effector T-cell.

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