Lymphoid tissue fibrosis is associated with impaired vaccine responses

J Clin Invest. 2018 Jul 2;128(7):2763-2773. doi: 10.1172/JCI97377. Epub 2018 May 21.

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.

Keywords: Adaptive immunity; Bacterial vaccines; Fibrosis; Immunology; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptive Immunity
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Clonal Anergy / immunology
  • Collagen / metabolism
  • Cytokines / blood
  • Female
  • Fibrosis
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV Seronegativity / immunology
  • Humans
  • Immune Tolerance
  • Lymphocyte Activation
  • Lymphoid Tissue / immunology*
  • Lymphoid Tissue / metabolism
  • Lymphoid Tissue / pathology*
  • Male
  • Middle Aged
  • Uganda
  • Vaccination*
  • Yellow Fever Vaccine / immunology
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Cytokines
  • Yellow Fever Vaccine
  • Collagen