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Infection and Immunity, August 2004, p. 4432-4438, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4432-4438.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Xisheng Wang,1 Hoil Kang,2,3,{dagger} Takane Kikuchi,1 and Yasuhiro Suzuki1,2,3*

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, Virginia 24061,1 Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305,2 Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, Palo Alto, California 943013

Received 11 February 2004/ Returned for modification 29 March 2004/ Accepted 8 April 2004

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.

* Corresponding author. Mailing address: 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, 1410 Prices Fork Rd., Blacksburg, VA 24061. Phone: (540) 231-2095. Fax: (540) 231-3426. E-mail: ysuzuki{at}vt.edu.

Editor: S. H. E. Kaufmann

{dagger} Present address: Department of Internal Medicine, Ageo Kosei Hospital, 421-1 Jitoukata, Ageo-Shi, Saitama 362-0051, Japan.

Infection and Immunity, August 2004, p. 4432-4438, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4432-4438.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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