Phenotypic and functional analysis of EBV-specific memory CD8 cells in SLE

Cell Immunol. 2005 May;235(1):29-38. doi: 10.1016/j.cellimm.2005.06.010. Epub 2005 Sep 19.

Abstract

T cell dysfunction has been described in systemic lupus erythematosus (SLE). However, the specific phenotype and function of antigen-specific CD8 cells is less clear. Here we determined phenotype and function of Epstein-Barr virus (EBV)-specific CD8 cells at the single-cell level in SLE. HLA-A2-restricted EBV-BMLF-1-specific CD8 cells were enumerated by flow cytometry using tetramers in SLE and healthy control subjects. Antigen-specific CD8 cells were analyzed for expression of differentiation, activation, proliferation, and anti-apoptotic markers. EBV-specific, other virus-specific (specific against a viral peptide pool consisting of cytomegalovirus, EBV and influenza virus peptides), and mitogen-induced CD8 cell function was assessed by INF-gamma ELISPOT assay. Frequencies of EBV-specific CD8 cells tended to be greater in SLE subjects than in healthy control subjects (p=0.07). While over 10% of EBV-specific CD8 cells were capable of producing IFN-gamma in four out of five healthy control subjects, such proportions of EBV-specific CD8 cells capable of IFN-gamma production were observed in only one out of six SLE subjects (p=0.04). In contrast, viral peptide pool-specific and mitogen-induced IFN-gamma-producing T cell function was intact in SLE subjects. Phenotypic analysis revealed EBV-specific CD8 cells to be in an early to intermediate differentiation and resting memory state in both groups. While EBV-specific CD8 cells are similar in phenotype, their frequency tends to be increased, and function appears to be decreased in SLE. Therefore, an impaired EBV-specific CD8 immune response may exist in SLE, potentially contributing to disease pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / physiology
  • Epitopes, T-Lymphocyte / analysis*
  • Epitopes, T-Lymphocyte / immunology
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunologic Memory*
  • Immunophenotyping*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / virology*
  • Middle Aged
  • Peptide Library
  • Phosphoproteins / analysis*
  • Phosphoproteins / immunology
  • Trans-Activators / analysis*
  • Trans-Activators / immunology
  • Viral Proteins / analysis*
  • Viral Proteins / immunology

Substances

  • Epitopes, T-Lymphocyte
  • Peptide Library
  • Phosphoproteins
  • SM protein, Human herpesvirus 4
  • Trans-Activators
  • Viral Proteins
  • Interferon-gamma