Heterogeneous and tissue-specific regulation of effector T cell responses by IFN-γ during Plasmodium berghei ANKA infection

Ana Villegas-Mendez, J. Brian De Souza, Linda Murungi, Julius C R Hafalla, Tovah N. Shaw, Rachel Greig, Eleanor M. Riley, Kevin N. Couper

    Research output: Contribution to journalArticlepeer-review

    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-γin 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. Copyright © 2011 by The American Association of Immunologists, Inc.
    Original languageEnglish
    Pages (from-to)2885-2897
    Number of pages12
    JournalJournal of Immunology
    Volume187
    Issue number6
    DOIs
    Publication statusPublished - 15 Sept 2011

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