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Altered immune cell follicular dynamics in HIV infection following influenza vaccination
Eirini Moysi, … , Constantinos Petrovas, Savita Pahwa
Eirini Moysi, … , Constantinos Petrovas, Savita Pahwa
Published June 18, 2018
Citation Information: J Clin Invest. 2018;128(7):3171-3185. https://doi.org/10.1172/JCI99884.
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Research Article AIDS/HIV Immunology

Altered immune cell follicular dynamics in HIV infection following influenza vaccination

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Abstract

HIV infection changes the lymph node (LN) tissue architecture, potentially impairing the immunologic response to antigenic challenge. The tissue-resident immune cell dynamics in virologically suppressed HIV+ patients on combination antiretroviral therapy (cART) are not clear. We obtained LN biopsies before and 10 to 14 days after trivalent seasonal influenza immunization from healthy controls (HCs) and HIV+ volunteers on cART to investigate CD4+ T follicular helper (Tfh) and B cell dynamics by flow cytometry and quantitative imaging analysis. Prior to vaccination, compared with those in HCs, HIV+ LNs exhibited an altered follicular architecture, but harbored higher numbers of Tfh cells and increased IgG+ follicular memory B cells. Moreover, Tfh cell numbers were dependent upon preservation of the follicular dendritic cell (FDC) network and were predictive of the magnitude of the vaccine-induced IgG responses. Interestingly, postvaccination LN samples in HIV+ participants had significantly (P = 0.0179) reduced Tfh cell numbers compared with prevaccination samples, without evidence for peripheral Tfh (pTfh) cell reduction. We conclude that influenza vaccination alters the cellularity of draining LNs of HIV+ persons in conjunction with development of antigen-specific humoral responses. The underlying mechanism of Tfh cell decline warrants further investigation, as it could bear implications for the rational design of HIV vaccines.

Authors

Eirini Moysi, Suresh Pallikkuth, Lesley R. De Armas, Louis E. Gonzalez, David Ambrozak, Varghese George, David Huddleston, Rajendra Pahwa, Richard A. Koup, Constantinos Petrovas, Savita Pahwa

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Figure 2

LN follicles with preserved FDC networks in treated HIV infection have higher absolute numbers of Tfh cells.

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LN follicles with preserved FDC networks in treated HIV infection have h...
(A) Representative confocal imaging examples showing the architecture of secondary follicles in HCs and HIV+ LNs. Tissue sections were stained with anti-CD20 (cyan) for B cell follicle identification, IgD (yellow) for the visualization of mantle zone, and the proliferation marker Ki67 (red) for dark zone/light zone delineation. MZ, mantle zone; LZ, light zone; DZ, dark zone. Scale bars: 50 μm. (B) Representative confocal imaging surface renderings of B cell follicles in treated HIV infection containing preserved (upper panels) or fragmented (lower panels) FDC networks. Scale bars: 50 μm; 30 μm (detail). (C) Linear regression plot showing the correlation between the total area of the FDC network in each follicle and absolute Tfh cell count as measured using histocytometry. Each dot represents an individual follicle, and follicles from a single tissue section are color coded according to patient ID (n = 4). Original magnification, ×40 (NA 1.3).
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