Opportunistic infections and retrovirus-induced immunodeficiency: studies of acute and chronic infections with Toxoplasma gondii in mice infected with LP-BM5 murine leukemia viruses.
Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-gamma) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with reduced proliferation and impaired production of IFN-gamma in response to stimulation with soluble T. gondii antigens or to concanavalin A. Continuing resistance to lethal reactivation in the remaining mice was shown to require CD8+ T cells and expression of IFN-gamma. In addition, it was found that chronic infection with T. gondii altered the course of MAIDS by inhibiting the progression of splenomegaly and immunodeficiency and reducing the expression of both the helper and etiologic defective viruses. These results support previous studies which indicate that infection with T. gondii is controlled by synergistic interactions between CD4+ and CD8+ T cells, the functions of which are progressively impaired during the course of MAIDS.
Gazzinelli
R T
RT
Immunology and Cell Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Hartley
J W
JW
Fredrickson
T N
TN
Chattopadhyay
S K
SK
Sher
A
A
Morse
H C
HC
D000208:Acute Disease; D000818:Animals; D016827:CD8 Antigens / Q000502:physiology; D002908:Chronic Disease; D005260:Female; D007109:Immunity; D007371:Interferon-gamma / Q000502:physiology; D009052:Leukemia Virus, Murine; D007942:Leukemia, Experimental / Q000276:immunology*; D051379:Mice; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology*; D009894:Opportunistic Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000150:complications / Q000276:immunology*
D016827:CD8 Antigens; D007371:Interferon-gamma