| First Author | Villegas-Mendez A | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 2 | Pages | 968-79 |
| PubMed ID | 22723523 | Mgi Jnum | J:189794 |
| Mgi Id | MGI:5447000 | Doi | 10.4049/jimmunol.1200688 |
| Citation | Villegas-Mendez A, et al. (2012) IFN-gamma-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain. J Immunol 189(2):968-79 |
| abstractText | It is well established that IFN-gamma is required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection of C57BL/6 mice. However, the temporal and tissue-specific cellular sources of IFN-gamma during P. berghei ANKA infection have not been investigated, and it is not known whether IFN-gamma production by a single cell type in isolation can induce cerebral pathology. In this study, using IFN-gamma reporter mice, we show that NK cells dominate the IFN-gamma response during the early stages of infection in the brain, but not in the spleen, before being replaced by CD4(+) and CD8(+) T cells. Importantly, we demonstrate that IFN-gamma-producing CD4(+) T cells, but not innate or CD8(+) T cells, can promote the development of ECM in normally resistant IFN-gamma(-/-) mice infected with P. berghei ANKA. Adoptively transferred wild-type CD4(+) T cells accumulate within the spleen, lung, and brain of IFN-gamma(-/-) mice and induce ECM through active IFN-gamma secretion, which increases the accumulation of endogenous IFN-gamma(-/-) CD8(+) T cells within the brain. Depletion of endogenous IFN-gamma(-/-) CD8(+) T cells abrogates the ability of wild-type CD4(+) T cells to promote ECM. Finally, we show that IFN-gamma production, specifically by CD4(+) T cells, is sufficient to induce expression of CXCL9 and CXCL10 within the brain, providing a mechanistic basis for the enhanced CD8(+) T cell accumulation. To our knowledge, these observations demonstrate, for the first time, the importance of and pathways by which IFN-gamma-producing CD4(+) T cells promote the development of ECM during P. berghei ANKA infection. |
