α-NAC-Specific Autoreactive CD8+ T Cells in Atopic Dermatitis Are of an Effector Memory Type and Secrete IL-4 and IFN-γ

J Immunol. 2016 Apr 15;196(8):3245-52. doi: 10.4049/jimmunol.1500351. Epub 2016 Mar 9.

Abstract

Autoreactivity may play a critical role in the chronification of atopic dermatitis (AD). Several studies showed that AD patients produce IgE Abs specific for autoantigens, and we described Th as well as CD8(+) T cells specific for the autoallergen Hom s 2, the α-chain of the nascent polypeptide-associated complex (α-NAC). This study aimed to investigate the frequency and inflammatory phenotype of autoallergen-specific CD8(+) T cells. CD8(+) T cell immunodominant epitopes of α-NAC were mapped by applying prediction softwares, and binding affinity was confirmed by stabilization of empty MHC complexes. MHC class I tetramers were assembled and binding cells were analyzed directly ex vivo by flow cytometry and in terms of single-cell assessment by ChipCytometry. We report significantly elevated numbers of α-NAC-specific peripheral T cells in sensitized patients compared with nonatopic controls. These cells secrete IL-4 and IFN-γ, and surface markers revealed significantly elevated frequencies of circulating terminally differentiated α-NAC-specific CD8(+) T cells in patients with AD compared with nonatopic donors. The observed phenotype of α-NAC-specific CD8(+) T cells indicates a role in the pathogenesis of AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Dermatitis, Atopic / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Flow Cytometry
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunoglobulin E / immunology
  • Immunologic Memory / immunology*
  • Interferon-gamma / metabolism*
  • Interleukin-4 / metabolism*
  • Molecular Chaperones / immunology*
  • Protein Binding / physiology

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A*02 antigen
  • HLA-A2 Antigen
  • IL4 protein, human
  • Molecular Chaperones
  • nascent-polypeptide-associated complex
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma