Gamma interferon production, but not perforin-mediated cytolytic activity, of T cells is required for prevention of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease.
We previously showed the requirement of both T cells and gamma interferon (IFN-gamma)-producing non-T cells for the genetic resistance of BALB/c mice to the development of toxoplasmic encephalitis (TE). In order to define the role of IFN-gamma production and the perforin-mediated cytotoxicity of T cells in this resistance, we obtained immune T cells from spleens of infected IFN-gamma knockout (IFN-gamma(-/-)), perforin knockout (PO), and wild-type BALB/c mice and transferred them into infected and sulfadiazine-treated athymic nude mice, which lack T cells but have IFN-gamma-producing non-T cells. Control nude mice that had not received any T cells developed severe TE and died after discontinuation of sulfadiazine treatment due to the reactivation of infection. Animals that had received immune T cells from either wild-type or PO mice did not develop TE and survived. In contrast, nude mice that had received immune T cells from IFN-gamma(-/-) mice developed severe TE and died as early as control nude mice. T cells obtained from the spleens of animals that had received either PO or wild-type T cells produced large amounts of IFN-gamma after stimulation with Toxoplasma gondii antigens in vitro. In addition, the amounts of IFN-gamma mRNA expressed in the brains of PO T-cell recipients did not differ from those in wild-type T-cell recipients. Furthermore, PO mice did not develop TE after infection, and their IFN-gamma production was equivalent to or higher than that of wild-type animals. These results indicate that IFN-gamma production, but not perforin-mediated cytotoxic activity, by T cells is required for the prevention of TE in genetically resistant BALB/c mice.
Wang
Xisheng
X
Center for Molecular Medicine and Infectious Diseases, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Kang
Hoil
H
Kikuchi
Takane
T
Suzuki
Yasuhiro
Y
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000469:parasitology; D004660:Encephalitis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014122:Toxoplasma / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000469:parasitology; D016781:Toxoplasmosis, Cerebral / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000469:parasitology
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma