Two alternate strategies for innate immunity to Epstein-Barr virus: One using NK cells and the other NK cells and γδ T cells

Author:

Djaoud Zakia12ORCID,Guethlein Lisbeth A.12ORCID,Horowitz Amir12,Azzi Tarik3ORCID,Nemat-Gorgani Neda12,Olive Daniel4ORCID,Nadal David3ORCID,Norman Paul J.12ORCID,Münz Christian5,Parham Peter12

Affiliation:

1. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305

2. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305

3. Experimental Infectious Disease and Cancer Research, Children’s Research Center, University Children’s Hospital of Zurich, 8032 Zurich, Switzerland

4. Team Immunity and Cancer, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut National de la Santé et de la Recherche Médicale, U1068; Centre National de la Recherche Scientifique, UMR7258, Institut Paoli-Calmettes; Aix-Marseille University, UM 105, 13284 Marseille, France

5. Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8006 Zurich, Switzerland

Abstract

Most humans become infected with Epstein–Barr virus (EBV), which then persists for life. Infrequently, EBV infection causes infectious mononucleosis (IM) or Burkitt lymphoma (BL). Type I EBV infection, particularly type I BL, stimulates strong responses of innate immune cells. Humans respond to EBV in two alternative ways. Of 24 individuals studied, 13 made strong NK and γδ T cell responses, whereas 11 made feeble γδ T cell responses but stronger NK cell responses. The difference does not correlate with sex, HLA type, or previous exposure to EBV or cytomegalovirus. Cohorts of EBV+ children and pediatric IM patients include both group 1 individuals, with high numbers of γδ T cells, and group 2 individuals, with low numbers. The even balance of groups 1 and 2 in the human population points to both forms of innate immune response to EBV having benefit for human survival. Correlating these distinctive responses with the progress of EBV infection might facilitate the management of EBV-mediated disease.

Funder

National Institutes of Health

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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