Impaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency

Begonia Morales-Aza, Sarah J Glennie, Tomaz Pereira Garcez, Victoria Davenport, Sarah L Johnston, Neil A Williams, Robert S Heyderman

Research output: Contribution to journalArticle (Academic Journal)peer-review

10 Citations (Scopus)

Abstract

The importance of T cells in the generation of antigen-specific B-cell immunity has been extensively described, but the role B cells play in shaping T-cell memory is uncertain. In healthy controls, exposure to Neisseria meningitidis in the upper respiratory tract is associated with the generation of memory T cells in the mucosal and systemic compartments. However, we demonstrate that in B cell-deficient subjects with X-linked agammaglobulinemia (XLA), naturally acquired T-cell memory responses to meningococcal antigens are reduced compared with healthy control patients. This difference is not found in T-cell memory to an obligate respiratory pathogen, influenza virus. Accordingly, we show that meningococcal antigens up-regulate major histocompatibility complex (MHC) class II, CD40, CD86/80 expression on mucosal and systemic associated B cells and that antigen presentation stimulates T-cell proliferation. A similar reduction in N meningitidis but not influenza antigen-specific T-cell memory was observed in subjects with X-linked hyper IgM syndrome (X-HIM), implicating the interaction of CD40-CD40L in this process. Together, these data implicate B cells in the induction and maintenance of T-cell memory to mucosal colonizing bacteria such as N meningitidis and highlight the importance of B cells beyond antibody production but as a target for immune reconstitution.
Translated title of the contributionImpaired maintenance of naturally acquired T-cell memory to the meningococcus in patients with B-cell immunodeficiency
Original languageEnglish
Pages (from-to)4206 - 4212
Number of pages7
JournalBlood
Volume113
Issue number18
DOIs
Publication statusPublished - 30 Apr 2009

Keywords

  • Young Adult
  • Antigens, CD40
  • Agammaglobulinemia
  • Humans
  • Hyper-IgM Immunodeficiency Syndrome, Type 1
  • Neisseria meningitidis
  • B-Lymphocytes
  • CD40 Ligand
  • Lymphocyte Activation
  • Meningococcal Infections
  • Adult
  • Antigens, Bacterial
  • Case-Control Studies
  • Genetic Diseases, X-Linked
  • Immunologic Memory
  • Middle Aged
  • Flow Cytometry
  • Male
  • Female
  • T-Lymphocytes

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