title: Natural killer cells recognize friend retrovirus-infected erythroid progenitor cells through NKG2D-RAE-1 interactions In Vivo.
abstract: Natural killer (NK) cells function as early effector cells in the innate immune defense against viral infections and also participate in the regulation of normal and malignant hematopoiesis. NK cell activities have been associated with early clearance of viremia in experimental simian immunodeficiency virus and clinical human immunodeficiency virus type 1 (HIV-1) infections. We have previously shown that NK cells function as major cytotoxic effector cells in vaccine-induced immune protection against Friend virus (FV)-induced leukemia, and NK cell depletion totally abrogates the above protective immunity. However, how NK cells recognize retrovirus-infected cells remains largely unclear. The present study demonstrates a correlation between the expression of the products of retinoic acid early transcript-1 (RAE-1) genes in target cells and their susceptibility to killing by NK cells isolated from FV-infected animals. This killing was abrogated by antibodies blocking the NKG2D receptor in vitro. Further, the expression of RAE-1 proteins on erythroblast surfaces increased early after FV inoculation, and administration of an RAE-1-blocking antibody resulted in increased spleen infectious centers and exaggerated pathology, indicating that FV-infected erythroid cells are recognized by NK cells mainly through the NKG2D-RAE-1 interactions in vivo. Enhanced retroviral replication due to host gene-targeting resulted in markedly increased RAE-1 expression in the absence of massive erythroid cell proliferation, indicating a direct role of retroviral replication in RAE-1 upregulation.
authors.affiliation: Department of Immunology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ogawa
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Tsuji-Kawahara
authors.forename: Takae
authors.initials: T
authors.lastname: Yuasa
authors.forename: Saori
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Tomomi
authors.initials: T
authors.lastname: Chikaishi
authors.forename: Shiki
authors.initials: S
authors.lastname: Takamura
authors.forename: Haruo
authors.initials: H
authors.lastname: Matsumura
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Saga
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000276:immunology* / Q000821:virology*; D005622:Friend murine leukemia virus / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*
chemical_list: D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse