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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

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-) 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- 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-. Together, these studies reveal that IL-2^-/- mice are unable to generate a protective IFN- response following infection with T. gondii and suggest that IL-2^-/- mice have an intrinsic defect in their ability to activate and expand IFN--producing T cells required for resistance to T. gondii.

Editor: J. M. Mansfield

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