PULMONARY LYMPHOID-CELL ACTIVATION AND CYTOKINE EXPRESSION IN MURINE AIDS-ASSOCIATED INTERSTITIAL PNEUMONITIS

Limited information is available about the pathogenesis of acquired im mune deficiency syndrome (AIDS)-associated idiopathic interstitial pne umonitis, a common noninfectious complication of human immunodeficienc y virus (HIV) infection. Infection of C57Bl/6 mice with LP-BM5 retrovi rus, a murine model of AIDS, leads to development of a diffuse interst itial pneumonitis that displays many features of human AIDS-associated interstitial pneumonitis. To further characterize the cellular and mo lecular features of this lung disease, the temporal development of cel lular infiltration, cytokine expression, and virus replication were ev aluated in lung tissue of virus-infected mice. Persistent expression o f viral RNA was detectable in lungs as early as 1 wk after infection. Infiltration of the lungs by CD4(+) and CD8(+) T cells, by IgG(+) and IgA(+) B cells, and by macrophages was observed by 4 wk after infectio n and continued through 8 wk of infection. Histologically, cellular in filtration was most pronounced in peribronchial and perivascular regio ns, whereas inflammation of alveolar septae and alveolar spaces was mi nimal. In contrast to normals, T cells from infected lungs were immuno deficient in that they failed to proliferate in response to the mitoge n concanavalin A (ConA). However, evaluation of cytokine mRNA expressi on by interstitial lung lymphoid cells indicated that cells from infec ted lungs were chronically activated, in that elevated expression of i nterferon-gamma (IFN-gamma) and interleukin 10 (IL-10) was observed th roughout the course of infection. Similarly, expression by interstitia l lung lymphoid cells of mRNA for the proinflammatory cytokine IL-1 an d the fibrogenic cytokine transforming growth factor-beta (TGF-beta) w as also increased following infection. These results indicate that ret rovirus-induced immunodeficiency in mice is associated with infiltrati on and chronic activation of lymphoid cells in the lungs. Furthermore, simultaneous expression of IL-10, IFN-gamma, and TGF-beta suggests th at cytokine-expressing cells in infected lungs may be unresponsive to inhibitory and antiinflammatory effects of IL-10 and/or TGF-beta, thus contributing to chronicity of inflammation in this disorder.