Dendritic and T cell response to influenza is normal in the patients with X-linked agammaglobulinemia

J Clin Immunol. 2012 Jun;32(3):421-9. doi: 10.1007/s10875-011-9639-y.

Abstract

Introduction: Influenza virus is a potential cause of severe disease in the immunocompromised. X-linked agammaglobulinemia(XLA) is a primary immunodeficiency characterized by the lack of immunoglobulin, B cells, and plasma cells,secondary to mutation in Bruton’s tyrosine kinase (Btk) gene. Btk is expressed in both B and dendritic cells (DC). However, little is known about the immune response of DC and T cells to influenza virus in XLA patients.

Methods: The in vitro maturation and antigen presenting function of monocyte-derived immature DC (im DC) from 12 XLA patients and 23 age-matched normal controls in response to influenza virus were examined. Influenza virus specific CD4 and CD8 T cell responses in the patients and controls were further determined after administration of inactivated trivalent influenza vaccine.

Results: im DC from XLA patients had normal maturation based on major histocompatibility complex (MHC)-I, MHCII, CD83 and CD86 expression, and interferon (IFN)-α and interleukin-12 production upon influenza virus stimulation.They also had a normal capacity to induce allogeneic T cell proliferation in response to influenza virus. TIV was well tolerated in XLA patients. Influenza virus-specific CD4+IFN-γ+ and CD8+ IFN-γ+ T cells and HLA-A2/M158–66-tetramer+ CTLs could be induced by TIV in XLA patients, and the levels and duration of maintaining these virus-specific cells in XLA patients are comparable to that in normal controls.

Conclusion: We demonstrated for the first time that XLA patients have fully competent DC and T cell immune responses to influenza virus. TIV is safe and could be an option for providing T cell-mediated protection against influenza virus infection in XLA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Agammaglobulinemia / immunology*
  • Case-Control Studies
  • Cell Differentiation
  • Cell Proliferation
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Genetic Diseases, X-Linked / immunology*
  • Humans
  • Influenza Vaccines / administration & dosage*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control
  • Interferon-alpha / immunology
  • Interleukin-12 / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Young Adult

Substances

  • Influenza Vaccines
  • Interferon-alpha
  • Interleukin-12

Supplementary concepts

  • Bruton type agammaglobulinemia