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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in immunology and vaccination

Regulation of effector T cell responses by IFN-γ during Plasmodium berghei ANKA infection.

LSHTM investigators:
Ana Villegas-Mendez, Brian de Souza, Tovah Shaw, Rachel Greig, Eleanor Riley & Kevin Couper.
Funding body:
Biotechnology and Biological Sciences Research Council.

IFN-g and T cells are both required for the development of experimental cerebral malaria during P. berghei ANKA infection but the role of IFN-g in shaping the effector CD4+ and CD8+ T cell response has not been examined in detail

To address this, we compared the effector T cell responses in wild-type and IFN- g-/- mice during P. berghei ANKA infection.  The expansion of splenic CD4+ and CD8+ T cells  was not affected by the absence of IFN-g but the contraction phase of the T cell response was significantly attenuated.  Splenic T cell activation and effector function were essentially normal in IFN- g-/- mice, however, the migration to, and accumulation of, effector CD4+ and CD8+ T cells in the lung, liver and brain was altered in IFN- g-/- mice.  Regulation of splenic T cell numbers depended upon active IFN- g-dependent environmental signals, leading to T cell apoptosis.  In summary, this study to reveals a novel role for IFN-γ during malaria infection, being required for efficient contraction of the pool of activated T cells upon resolution of the infection.