Heterogeneous and Tissue-Specific Regulation of Effector T Cell Responses by IFN-{gamma} during Plasmodium berghei ANKA Infection.


Villegas-Mendez, A; de Souza, JB; Murungi, L; Hafalla, JC; Shaw, TN; Greig, R; Riley, EM; Couper, KN; (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. 2885-97. ISSN 0022-1767 DOI: https://doi.org/10.4049/jimmunol.1100241

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Abstract

IFN-? and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-? 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-?(-/-) 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-?, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-?(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-?(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-?, suggesting that IFN-? 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-?-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-? in modulating T cell function during P. berghei ANKA infection and reveals that IFN-? is required for efficient contraction of the pool of activated T cells.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Malaria Centre
PubMed ID: 21880980
Web of Science ID: 295034200007
URI: http://researchonline.lshtm.ac.uk/id/eprint/221

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