Lymphoid tissue fibrosis is associated with impaired vaccine responses

• Type of Material: Article
• Authors: Cissy Kityo, Joint Clinical Research Center; Krystelle Nganou Makamdop, National Institute of Allergy and Infectious Diseases; Meghan Rothenberger, University of Minnesota; Jeffrey G. Chipman, University of Minnesota; Torfi Hoskuldsson, University of Minnesota; Gregory J. Beilman, University of Minnesota; Bartosz Grzywacz, University of Minnesota; Peter Mugyenyi, Joint Clinical Research Center; Francis Ssali, Joint Clinical Research Center; Rama Akondy, Emory University; Jodi Anderson, University of Minnesota; Thomas E. Schmidt, University of Minnesota; Thomas Reimann, University of Minnesota; Samuel P. Callisto, University of Minnesota; Jordan Schoephoerster, University of Minnesota; Jared Schuster, University of Minnesota; Proscovia Muloma, Joint Clinical Research Center; Patrick Ssengendo, Joint Clinical Research Center; Eirini Moysi, National Institute of Allergy and Infectious Diseases; Constantinos Petrovas, National Institute of Allergy and Infectious Diseases; Ray Lanciotti, Centers for Disease Control and Prevention; Lin Zhang, University of Minnesota; Maria T. Arevalo, University of Georgia; Benigno Rodriguez, Case Western Reserve University; Ted M. Ross, University of Georgia; Lydie Trautmann, Walter Reed Army Institute of Research; Rafick-Pierre Sekaly, Case Western Reserve University; Michael M. Lederman, Case Western Reserve University; Richard A. Koup, National Institute of Allergy and Infectious Diseases; Rafi Ahmed, Emory University; Cavan Reilly, University of Minnesota; Daniel C. Douek, National Institute of Allergy and Infectious Diseases; Timothy W. Schacker, University of Minnesota
• Language: English
• Date: 2018-07-02
• Publisher: American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2018 American Society for Clinical Investigation. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1172/JCI97377
• Title of Journal or Parent Work: Journal of Clinical Investigation
• ISSN: 0021-9738
• Volume: 128
• Issue: 7
• Start Page: 2763
• End Page: 2773
• Grant/Funding Information: The views expressed herein are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense.; This work was supported in part by grants NIH AI074340, NIH UL1TR000114, NIH AI093319, and NIH AI036219, and by the intramural program of the National Institutes of Health.
• Keywords: Life Sciences & Biomedicine; ORAL POLIO VACCINATION; IMMUNODEFICIENCY VIRUS-INFECTION; ANTIBODY-RESPONSE; COLLAGEN DEPOSITION; FIBROBLASTIC RETICULAR CELLS; Medicine, Research & Experimental; ROTAVIRUS VACCINE; T-CELLS; Science & Technology; IMMUNE RECONSTITUTION; HUMORAL RESPONSES; ANTIRETROVIRAL THERAPY; Research & Experimental Medicine
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. We hypothesized that other infections may cause LN inflammation and fibrosis, in a process similar to that seen in HIV infection, which may lead to T cell depletion and affect vaccine responses. We studied LNs of individuals from Kampala, Uganda, before and after yellow fever vaccination (YFV) and found fibrosis in LNs that was similar to that seen in HIV infection. We found blunted antibody responses to YFV that correlated to the amount of LN fibrosis and loss of T cells, including T follicular helper cells. These data suggest that LN fibrosis is not limited to HIV infection and may be associated with impaired immunologic responses to vaccines. This may have an impact on vaccine development, especially for infectious diseases prevalent in the developing world.