Control of pathogenic CD8+ T cell migration to the brain by IFN-gamma during experimental cerebral malaria.
Previous studies have shown that IFN-gamma is essential for the pathogenesis of cerebral malaria (CM) induced by Plasmodium berghei ANKA (PbA) in mice. However, the exact role of IFN-gamma in the pathway (s) leading to CM has not yet been described. Here, we used 129P2Sv/ev mice which develop CM between 7 and 14 days post-infection with PbA. In this strain, both CD4(+) and CD8(+) T cells were involved in the effector phase of CM. When 129P2Sv/ev mice deficient in the IFN-gamma receptor alpha chain (IFN-gammaR1) were infected with PbA, CM did not occur. Migration of leucocytes to the brain at the time of CM was observed in wild type (WT) but not in deficient mice. However, in the latter, there was an accumulation of T cells in the lungs. Analysis of chemokines and their receptors in WT and in deficient mice revealed a complex, organ-specific pattern of expression. Up-regulation of RANTES/CCL5, IP-10/CCL3 and CCR2 was associated with leucocyte migration to the brain and increased expression of MCP-1/CCL2, IP-10/CCL3 and CCR5 with leucocyte migration to the lung. This shows that IFN-gamma controls trafficking of pathogenic T cells in the brain, thus providing an explanation for the organ-specific pathology induced by PbA infection.
Belnoue
E
E
Department of Immunology, Institute Cochin, Université Paris Descartes, CNRS UMR 8104, Paris, France.
Potter
S M
SM
Rosa
D S
DS
Mauduit
M
M
Grüner
A C
AC
Kayibanda
M
M
Mitchell
A J
AJ
Hunt
N H
NH
Rénia
L
L
D000818:Animals; D001921:Brain / Q000276:immunology / Q000469:parasitology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002465:Cell Movement; D018925:Chemokines / Q000276:immunology; D015870:Gene Expression; D007371:Interferon-gamma / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000469:parasitology; D016779:Malaria, Cerebral / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000469:parasitology; D010962:Plasmodium berghei / Q000276:immunology*; D012313:RNA / Q000235:genetics; D019707:Receptors, Chemokine / Q000276:immunology; D017471:Receptors, Interferon / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D000096743:Interferon gamma Receptor
D018925:Chemokines; D007371:Interferon-gamma; D012313:RNA; D019707:Receptors, Chemokine; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor