Lymphoid tissue fibrosis is associated with impaired vaccine responses

Cissy Kityo, Krystelle Nganou Makamdop, Meghan K Rothenberger, Jeffrey G Chipman, Torfi Hoskuldsson, Gregory J Beilman, Bartosz J Grzywacz, Peter Mugyenyi, Francis Ssali, Rama S. Akondy, Jodi Anderson, Thomas E. Schmidt, Thomas Reimann, Samuel P. Callisto, Jordan Schoephoerster, Jared Schuster, Proscovia Muloma, Patrick Ssengendo, Eirini Moysi, Constantinos PetrovasRay Lanciotti, Lin Zhang, Maria T. Arévalo, Benigno Rodriguez, Ted M. Ross, Lydie Trautmann, Rafick Pierre Sekaly, Michael M. Lederman, Richard A. Koup, Rafi Ahmed, Cavan S Reilly, Daniel C. Douek, Timothy W Schacker

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2763-2773
Number of pages11
JournalJournal of Clinical Investigation
Volume128
Issue number7
DOIs
StatePublished - Jul 2 2018

Bibliographical note

Funding Information:
We thank Ashley Haase (University of Minnesota) for his support and advice and Deborah Powell (University of Minnesota) for her encouragement and financial support to initiate this project. We also thank Deborah Masiira, G. Namayanja, J. Kabanda, H. Musa-na, Rose Byaruhanga, Milly Ndigendawani, Ezra Lutalo, Sofia Kasuswa, Charles Isabirye, Nicholas Karamagi, and Baonzi Necion for their advice and support (all from Joint Clinical Research Center in Kampala, Uganda). 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. 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.

Publisher Copyright:
© 2018 American Society for Clinical Investigation. All rights reserved.

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