Mechanisms accounting for granulomatous responses in hypersensitivity pneumonitis.

Hypersensitivity granuloma formation is an immunopathological feature of HP. It is induced by the T cell-mediated delayed-type hypersensitivity reaction to organic dusts or active chemicals invading the lung. Circulating, antigen-reactive, memory CD4+ T cells, generated by previous sensitization, migrate into lung parenchyma in response to chemokines such as RANTES. The T cells develop into either Th0, Th1, or Th2 effector depending upon the conditions in which they first encounter the antigens. The Th1 cells produce IL-2 and IFN-gamma. IFN-gamma can prime macrophages to transcribe and to secrete greater amounts of TNF and IL-1. The macrophages activated by TNF and IL-1 produce a wide range of biologically active mediators such as MAF, MCF, and MIF. These monokines attract young macrophages into the lesions, activate them, and young macrophages develop into mature macrophages, resulting in the hypersensitivity granuloma consisting of epithelioid cells and multinucleated giant cells. CD8+ T cells, the most predominant cell in the lesions of HP, may modulate the granuloma formation via the production of Th1-like or Th2-like cytokines.