Role of T cell subsets in the development of AIDS-associated interstitial pneumonitis in mice.
Idiopathic interstitial pneumonitis (IP), characterized by lymphocytic infiltration of the lung and pulmonary dysfunction, is a major noninfectious complication of human immunodeficiency virus (HIV) infection. The role of the CD4+ and CD8+ T cell populations and INF-gamma in the development of IP were analyzed using a murine model of retroviral-associated IP. Infected mice depleted of CD8+ T cells developed IP similarly to untreated infected mice, suggesting that the CD8+ T cell population does not play a role in IP. Furthermore, depletion of CD8+ T cells did not alter the level of viral RNA in lungs, suggesting that cytotoxic T cells may not serve a role in controlling virus burden in lungs. In contrast, depletion of CD4+ T cells in infected mice prevented the development of IP and inhibited inflammatory cytokine expression, suggesting that CD4+ T cells are important for the development of IP. IFN-gamma -/- mice infected with virus for 10 weeks developed IP, although the severity of lymphocytic infiltration was substantially reduced compared to infected wild-type mice. The data suggest that persistent viral antigen in the lung may drive a CD4+ T cell-mediated immune response, resulting in the chronic production of IFN-gamma which amplifies a chronic inflammatory response in the lung resulting in tissue injury.
Fitzpatrick
E A
EA
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536-0084, USA.
Avdiushko
M
M
Kaplan
A M
AM
Cohen
D A
DA
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006378:Helper Viruses / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000502:physiology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017563:Lung Diseases, Interstitial / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008908:Mink Cell Focus-Inducing Viruses / Q000502:physiology; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014779:Virus Replication
D016207:Cytokines; D007371:Interferon-gamma