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- DOI: 10.4049/jimmunol.1100241
- PMID: 21880980
- UKPMCID: 21880980
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Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-y during Plasmodium berghei ANKA infection.
Villegas-Mendez, Ana; de Souza, J Brian; Murungi, Linda; Hafalla, Julius C R; Shaw, Tovah N; Greig, Rachel; Riley, Eleanor M; Couper, Kevin N
Journal of immunology. 2011;187(6):2885.
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Full-text held externally
- DOI: 10.4049/jimmunol.1100241
- PMID: 21880980
- UKPMCID: 21880980
Abstract
IFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells.
Bibliographic metadata
- 041611, Biotechnology and Biological Sciences Research Council, United Kingdom
- 074538, Wellcome Trust, United Kingdom
- 074538, Wellcome Trust, United Kingdom
- BB/G004161/1, Biotechnology and Biological Sciences Research Council, United Kingdom
- G0900487, Medical Research Council, United Kingdom
- G0900487(91552), Medical Research Council, United Kingdom