Altered immune cell follicular dynamics in HIV infection following influenza vaccination

J Clin Invest. 2018 Jul 2;128(7):3171-3185. doi: 10.1172/JCI99884. Epub 2018 Jun 18.

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.

Keywords: AIDS vaccine; AIDS/HIV; B cells; Immunology; T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Case-Control Studies
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / pathology
  • Humans
  • Influenza Vaccines / immunology*
  • Lymph Nodes / immunology*
  • Lymph Nodes / pathology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • T-Lymphocytes, Helper-Inducer / classification
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / pathology
  • Vaccination

Substances

  • Influenza Vaccines