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

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 (imDC) 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: imDC from XLA patients had normal maturation based on major histocompatibility complex (MHC)-I, MHC-II, 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/M1 58-66-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. © 2012 The Author(s).