title: Low Thymic Activity and Dendritic Cell Numbers Are Associated with the Immune Response to Primary Viral Infection in Elderly Humans.
abstract: Immunological competence declines progressively with age, resulting in increased susceptibility of the elderly to infection and impaired responses to vaccines. Underlying mechanisms remain largely obscure as they have been related to complex, individual systemic immune properties that are challenging to investigate. In this study, we explored age-related changes in human immunity during a primary virus infection experimentally induced by immunization with live-attenuated yellow fever (YF) vaccine. Applying detailed serology, advanced FACS analysis, and systems biology, we discovered that aged subjects developed fewer neutralizing Abs, mounted diminished YF-specific CD8(+) T cell responses, and showed quantitatively and qualitatively altered YF-specific CD4(+) T cell immunity. Among numerous immune signatures, low in vivo numbers of naive CD4(+) recent thymic emigrants and peripheral dendritic cells correlated well with reduced acute responsiveness and altered long-term persistence of human cellular immunity to YF vaccination. Hence, we reveal in this article that essential elements of immune responses such as recent thymic emigrants and dendritic cells strongly relate to productive immunity in the elderly, providing a conceivable explanation for diminished responsiveness to vaccination with neoantigens and infection with de novo pathogens in the aged population.
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow-Klinikum, 13353 Berlin, Germany; Immune Monitoring Core, German Rheumatism Research Centre Berlin (a Leibniz Institute), D-10117 Berlin, Germany; axel.schulz@drfz.de.
authors.forename: Axel Ronald
authors.identifier: http://orcid.org/0000-0002-5106-0148
authors.initials: AR
authors.lastname: Schulz
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow-Klinikum, 13353 Berlin, Germany;
authors.forename: Julia Nora
authors.initials: JN
authors.lastname: Mälzer
authors.affiliation: Center for Biological Threats and Special Pathogens 1 - Highly Pathogenic Viruses, Robert Koch Institute, 13353 Berlin, Germany;
authors.forename: Cristina
authors.initials: C
authors.lastname: Domingo
authors.affiliation: Systems Biology of Infectious Diseases, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow-Klinikum, 13353 Berlin, Germany;
authors.forename: Karsten
authors.initials: K
authors.lastname: Jürchott
authors.affiliation: Immune Monitoring Core, German Rheumatism Research Centre Berlin (a Leibniz Institute), D-10117 Berlin, Germany; axel.schulz@drfz.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Grützkau
authors.affiliation: Renal and Transplant Research Unit, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow-Klinikum, 13353 Berlin, Germany; and.
authors.forename: Nina
authors.initials: N
authors.lastname: Babel
authors.affiliation: Renal and Transplant Research Unit, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow-Klinikum, 13353 Berlin, Germany; and.
authors.forename: Mikalai
authors.identifier: http://orcid.org/0000-0002-5678-1956
authors.initials: M
authors.lastname: Nienen
authors.affiliation: Berlin Center for Travel and Tropical Medicine, 10117 Berlin, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Jelinek
authors.affiliation: Center for Biological Threats and Special Pathogens 1 - Highly Pathogenic Viruses, Robert Koch Institute, 13353 Berlin, Germany;
authors.forename: Matthias
authors.identifier: http://orcid.org/0000-0001-7965-4872
authors.initials: M
authors.lastname: Niedrig
authors.affiliation: Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Campus Virchow-Klinikum, 13353 Berlin, Germany;
authors.forename: Andreas
authors.initials: A
authors.lastname: Thiel
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007121:Immunocompetence / Q000276:immunology / Q000502:physiology; D007074:Immunoglobulin G / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D013950:Thymus Gland / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014766:Viremia / Q000276:immunology; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D022341:Yellow Fever Vaccine