Leishmania major infection in interleukin-4 and interferon-gamma depleted mice.
The outcome of experimental Leishmania major infection in mice is closely correlated with the type of CD4+ helper T cell (Th) response. Whereas a Th1 response is host protective, a Th2 response leads to a disseminated, fatal course of disease. Previous studies in this murine model have shown, that the two prominent Th1 and Th2 cytokines, interferon (IFN)-gamma and interleukin (IL)-4, themselves play a major role in the determination of the resulting Th response. Treatment of susceptible mouse strains (BALB/c) with anti-IL-4 induces a Th1 response, allowing the animals to cure the infection. Treatment of resistant strains (e.g. C3H/HeN) with anti-IFN-gamma induces a Th2 response with dissemination of the disease. In this report, we investigated the course of infection and Th response in susceptible and resistant mice treated with anti-IL-4 and anti-IFN-gamma simultaneously. Both mouse strains showed an initial exacerbation of the disease and an overall reduced cytokine response early after infection. Later during infection both strains had a strong Th1 response that was resulting in cure of disease in C3H/HeN mice. BALB/c mice however, could not control the spread of infection despite the strong Th1 response.
Chatelain
R
R
Department of Dermatology, Laboratory for Immunodermatology, Ludwig-Maximilians-University, Munich, Germany.
Mauze
S
S
Varkila
K
K
Coffman
R L
RL
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000953:Antigens, Protozoan / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology*; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D000906:Antibodies; D000953:Antigens, Protozoan; D015847:Interleukin-4; D007371:Interferon-gamma