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Lymphoid tissue fibrosis is associated with impaired vaccine responses
Cissy Kityo, … , Daniel C. Douek, Timothy W. Schacker
Cissy Kityo, … , Daniel C. Douek, Timothy W. Schacker
Published May 21, 2018
Citation Information: J Clin Invest. 2018;128(7):2763-2773. https://doi.org/10.1172/JCI97377.
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Research Article Immunology

Lymphoid tissue fibrosis is associated with impaired vaccine responses

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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.

Authors

Cissy Kityo, Krystelle Nganou Makamdop, Meghan Rothenberger, Jeffrey G. Chipman, Torfi Hoskuldsson, Gregory J. Beilman, Bartosz 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 Petrovas, Ray 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 Reilly, Daniel C. Douek, Timothy W. Schacker

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Figure 7

B cell follicles are diminished and there is a paucity of T follicular helper cells in B cell follicles in Ugandans.

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B cell follicles are diminished and there is a paucity of T follicular h...
This figure shows LN analysis from 3 different participants before vaccination and again at week 2 after vaccination. Participant 1996 has recognizable follicles before vaccination and formation of follicles after vaccination. The accumulation of PD1 staining cells within the secondary follicle (D) with green and blue staining cells in the secondary follicle (staining yellow) show an expected reaction to vaccination. Panel B shows participant 1682 with fewer, more poorly formed follicles at baseline and a lack of recognizable secondary follicles with vaccination. PD1 staining cells are not inside of the follicle structure. Participant 1688 has no recognizable follicles prior to vaccination and no response to vaccination. Scale bar indicates 20 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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