Impaired Peripheral Blood T-follicular Helper Cell Function in HIV-infected Nonresponders to the 2009 H1N1/09 Vaccine

Blood. 2012 Aug 2;120(5):985-93. doi: 10.1182/blood-2011-12-396648. Epub 2012 Jun 12.

Abstract

The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5(+) CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and CD4 T-cell loss are recognized features of HIV infection, in the present study, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HCs), and these cells displayed a central memory phenotype. Sixteen patients and 8 HCs in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responders (n = 8) and HCs, pTFH cells underwent expansion with increased IL-21 and CXCL13 secretion in H1N1-stimulated PBMC culture supernatants at week 4 (T2). These changes were not seen in vaccine nonresponders (n = 8). In coculture experiments, sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH were correlated with memory B cells, serum H1N1 Ab titers, and Ag-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight into cellular determinants of vaccine-induced Ab response, which may have relevance for vaccine design.

Publication types

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

MeSH terms

  • Adult
  • Antibody Formation / physiology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology
  • Case-Control Studies
  • Cell Differentiation
  • Cells, Cultured
  • Follow-Up Studies
  • HIV Infections / blood
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV Infections / therapy
  • HIV-1 / physiology
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / therapeutic use*
  • Influenza, Human / blood
  • Influenza, Human / complications
  • Influenza, Human / immunology
  • Influenza, Human / therapy*
  • Middle Aged
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / pathology
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Treatment Failure
  • Young Adult

Substances

  • Influenza Vaccines