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Infection and Immunity, September 2002, p. 4757-4761, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4757-4761.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Susceptibility of Interleukin-2-Deficient Mice to Toxoplasma gondii Is Associated with a Defect in the Production of Gamma Interferon

Eric N. Villegas,1 Linda A. Lieberman,1 Simon R. Carding,2 and Christopher A. Hunter1*

Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia 19104-6050, Pennsylvania,1 School of Biochemistry and Molecular Biology, The University of Leeds, Leeds, LS2 9JT, West Yorkshire, England2

Received 7 January 2002/ Returned for modification 2 April 2002/ Accepted 22 May 2002

Costimulation through the B7-CD28 interaction is an important second signal for T-cell activation, and previous studies have shown that CD28-/- mice infected with Toxoplasma gondii generate suboptimal CD4+ T-cell responses, associated with a defect in production of the T-cell growth factor interleukin-2 (IL-2). To address the role of IL-2 in the expansion of T cells during toxoplasmosis, IL-2-/- mice were infected with T. gondii and their ability to generate a protective T-cell response was assessed. Although IL-2-/- mice produced normal levels of IL-12p40, they had reduced levels of gamma interferon (IFN-{gamma}) in serum, had an increased parasite burden, and succumbed to infection with T. gondii within 20 days. Fluorescence-activated cell sorter analysis revealed that, although uninfected IL-2-/- mice had an increased number of activated T cells compared with uninfected IL-2+/+ mice, following infection they were unable to further upregulate this population. Examination of the ability of splenocytes from uninfected and infected mice to produce IFN-{gamma} revealed that IL-2-/- mice were hyporesponsive to stimulation with anti-CD3 or parasite antigen compared with wild-type mice, and the addition of IL-2 alone or in combination with IL-12 or stimulation with phorbol myristate acetate and ionomycin did not restore the production of IFN-{gamma}. Together, these studies reveal that IL-2-/- mice are unable to generate a protective IFN-{gamma} response following infection with T. gondii and suggest that IL-2-/- mice have an intrinsic defect in their ability to activate and expand IFN-{gamma}-producing T cells required for resistance to T. gondii.

* Corresponding author. Mailing address: Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Room 226 Rosenthal Building, 3800 Spruce St., Philadelphia, PA 19104-6008. Phone: (215) 573-7772. Fax: (215) 573-7023. E-mail: chunter{at}vet.upenn.edu.

Editor: J. M. Mansfield

Infection and Immunity, September 2002, p. 4757-4761, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.4757-4761.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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