NK cells protect secondary lymphoid tissue from cytomegalovirus via a CD30-dependent mechanism.
The pathogenic outcomes of viral infection are often reminiscent of a dysfunctional immune system. Thus, cytomegalovirus (CMV) causes disruption of the lymphoid architecture and the functionality of lymphocytes, both of which are features of CD30 deficiency. It was therefore plausible that CD30 might interfere with CMV infection. The present study identifies CD30 as an inducible NK-cell receptor critical for innate immunity against CMV. Expression of CD30 integrates survival signals to NK cells that allow them to prevent viral spread and subsequent disintegration of secondary lymphoid tissue. Deficiency in CD30 results in exaggerated NK cell death and complete abrogation of the lymphoid architecture. Our data define the necessity of NK cells for protection of secondary lymphoid organs and describe a mechanism by which this protection is conferred.
Bekiaris
Vasileios
V
Medical Research Council Centre for Immune Regulation, School of Medicine, University of Birmingham, Birmingham, UK. vbekiaris@liai.org
Gaspal
Fabrina
F
McConnell
Fiona M
FM
Kim
Mi-Yeon
MY
Withers
David R
DR
Sweet
Clive
C
Anderson
Graham
G
Lane
Peter J L
PJ
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D053285:CD30 Ligand / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018398:Homeodomain Proteins / Q000235:genetics; D007113:Immunity, Innate / Q000502:physiology*; D017730:Ki-1 Antigen / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D018146:Muromegalovirus / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D039521:CD11c Antigen; D053285:CD30 Ligand; D018398:Homeodomain Proteins; D017730:Ki-1 Antigen; C527096:Klra8 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A; C505775:Tnfsf8 protein, mouse; D019010:Vascular Cell Adhesion Molecule-1; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens