The chemokine receptor CXCR6 is required for the maintenance of liver memory CD8⁺ T cells specific for infectious pathogens.
It is well established that immunization with attenuated malaria sporozoites induces CD8(+) T cells that eliminate parasite-infected hepatocytes. Liver memory CD8(+) T cells induced by immunization with parasites undergo a unique differentiation program and have enhanced expression of CXCR6. Following immunization with malaria parasites, CXCR6-deficient memory CD8(+) T cells recovered from the liver display altered cell-surface expression markers as compared to their wild-type counterparts, but they exhibit normal cytokine secretion and expression of cytotoxic mediators on a per-cell basis. Most importantly, CXCR6-deficient CD8(+) T cells migrate to the liver normally after immunization with Plasmodium sporozoites or vaccinia virus, but a few weeks later their numbers severely decrease in this organ, losing their capacity to inhibit malaria parasite development in the liver. These studies are the first to show that CXCR6 is critical for the development and maintenance of protective memory CD8(+) T cells in the liver.
Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Sze-Wah
SW
Tse
Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Andrea J
AJ
Radtke
Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Diego A
DA
Espinosa
Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University, Canberra.
Ian A
IA
Cockburn
Department of Molecular Microbiology and Immunology and Johns Hopkins Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Fidel
F
Zavala
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000502:physiology*; D008109:Liver Diseases, Parasitic / Q000276:immunology*; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010962:Plasmodium berghei / Q000276:immunology; D054387:Receptors, CXCR / Q000502:physiology*; D000075744:Receptors, CXCR6
C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6
Plasmodium; chemokine receptor; liver; malaria; memory CD8+ T cells