Villegas-Mendez, Ana; de Souza, J Brian; Murungi, Linda; Hafalla, Julius CR; Shaw, Tovah N; Greig, Rachel; Riley, Eleanor M; Couper, Kevin N; (2011) Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection. Journal of immunology (Baltimore, Md, 187 (6). pp. 2885-2897. ISSN 0022-1767 DOI: https://doi.org/10.4049/jimmunol.1100241
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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.
Item Type | Article |
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Faculty and Department |
Faculty of Infectious and Tropical Diseases > Department of Infection Biology Faculty of Infectious and Tropical Diseases > Department of Infection Biology > Dept of Immunology and Infection (-2019) |
Research Centre | Malaria Centre |
PubMed ID | 21880980 |
ISI | 295034200007 |
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