Am. J. Respir. Cell Mol. Biol., Vol 16, No. 2, Feb 1997, 153-161.
Pulmonary lymphoid cell activation and cytokine expression in murine AIDS-associated interstitial pneumonitis
DA Cohen, EA Fitzpatrick, C Hartsfield, MN Gillespie, M Avdiushko and AM Kaplan
Department of Microbiology and Immunology, College of Medicine, University of Kentucky Medical Center, Lexington 40536-0084, USA.
Limited information is available about the pathogenesis of acquired immune
deficiency syndrome (AIDS)-associated idiopathic interstitial pneumonitis,
a common noninfectious complication of human immunodeficiency virus (HIV)
infection. Infection of C57B1/6 mice with LP-BM5 retrovirus, a murine model
of AIDS, leads to development of a diffuse interstitial pneumonitis that
displays many features of human AIDS-associated interstitial pneumonitis.
To further characterize the cellular and molecular features of this lung
disease, the temporal development of cellular infiltration, cytokine
expression, and virus replication were evaluated in lung tissue of
virus-infected mice. Persistent expression of 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 infection and continued through 8 wk of infection.
Histologically, cellular infiltration was most pronounced in peribronchial
and perivascular regions, whereas inflammation of alveolar septae and
alveolar spaces was minimal. In contrast to normals, T cells from infected
lungs were immunodeficient in that they failed to proliferate in response
to the mitogen concanavalin A (ConA). However, evaluation of cytokine mRNA
expression by interstitial lung lymphoid cells indicated that cells from
infected lungs were chronically activated, in that elevated expression of
interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) was observed
throughout the course of infection. Similarly, expression by interstitial
lung lymphoid cells of mRNA for the proinflammatory cytokine IL-1 and the
fibrogenic cytokine transforming growth factor-beta (TGF-beta) was also
increased following infection. These results indicate that retrovirus-
induced immunodeficiency in mice is associated with infiltration and
chronic activation of lymphoid cells in the lungs. Furthermore,
simultaneous expression of IL-10, IFN-gamma, and TGF-beta suggests that
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.
