Susceptibility of Interleukin-2-Deficient Mice toToxoplasma gondiiIs Associated with a Defect in the Production of Gamma Interferon
Year: 2002
Type: article
Abstract: 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.
Source: Infection and Immunity
Institutions: University of Pennsylvania, University of Leeds
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1052914552, ORIGIN AND DEVELOPMENT OF HUMAN GD T-CELLS, G1201263685, G158792630, G1663719654, G1686704731, G3518525861, GUT FLORA AS A PROVOCATEUR OF AUTOIMMUNE COLITIS, Immunopathogenesis of Toxoplasmic encephalitis, Regulation of the early immune response to toxoplasma gondii, G6803554947, G688549174, MINORITY PREDOCTORAL FELLOWSHIP PROGRAM, G9000136813
OpenAlex ID: W2127548152