Modulation of murine AIDS-related pathology by concurrent antibody treatment and coinfection with Leishmania major.
Infection of C57BL/6 mice with a mixture of murine leukemia viruses (MuLVs) designated LP-BM5 MuLV leads to a disease characterized by progressive immunodeficiency and lymphoproliferation, known as murine AIDS (MAIDS). The development of MAIDS is associated with increased B-cell lymphoblast proliferation, but there is reason to believe that T-cell function and, particularly, T-cell-derived cytokines may also play a role. We have previously shown that concurrent infection with Leishmania major (which induces a strongly polarized Th1 response in C57BL/6 mice) and LP-BM5 MuLV modulates the disease induced by both infections. Here we show by treatment of mice with anticytokine antibodies that this modulation is largely exerted through the balance of Th1 and Th2 cytokines. Infected mice treated with antibodies to interleukin-4 and interleukin-10 exhibited a delayed development of MAIDS-related pathology and maintained T-cell responsiveness longer than mice treated with control antibody. Gamma interferon induced by coinfection with L. major synergized with anti-IL-4 treatment to inhibit the development of MAIDS pathology. Conversely, treatment with anti-gamma interferon led to a significant increase in splenomegaly and lymphadenopathy and slightly exacerbated loss of T-cell function. These data suggest that the production of Th2-associated cytokines may promote MAIDS pathology, while Th1-associated cytokines may help control the disease.
Doherty
T M
TM
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Giese
N
N
Morse
H C
HC
Coffman
R L
RL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016207:Cytokines / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma