Phenotypic and functional analysis of EBV-specific memory CD8 cells in SLE.
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.
Berner
Beate R
BR
Department of Pathology, The Center for AIDS Research, Case Western Reserve University, University Hospitals of Cleveland, The Veterans Administration Medical Center, Cleveland, OH, USA. beate.berner@med.uni-tnebingen.de
Tary-Lehmann
Magdalena
M
Yonkers
Nicole L
NL
Askari
Ali D
AD
Lehmann
Paul V
PV
Anthony
Donald D
DD
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008875:Middle Aged; D019151:Peptide Library; D010750:Phosphoproteins / Q000032:analysis* / Q000276:immunology; D015534:Trans-Activators / Q000032:analysis* / Q000276:immunology; D014764:Viral Proteins / Q000032:analysis* / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D019151:Peptide Library; D010750:Phosphoproteins; C090236:SM protein, Human herpesvirus 4; D015534:Trans-Activators; D014764:Viral Proteins; D007371:Interferon-gamma