Restricted diversification of T-cells in chronic active Epstein-Barr virus infection: Potential inclination to T-lymphoproliferative disease

Abstract

To assess the abnormal T-cell expansion in chronic active Epstein-Barr virus infection (CAEBV), T-cell antigen receptor (TCR) repertoire was analyzed in four patients with the disease. All fulfilled the diagnostic criteria of CAEBV, presenting with fever, hepatosplenomegaly, cytopenia, abnormal high titers of anti EBV-antibodies, and positive EBV genome of unknown cause. Southern blotting probed with EBV-terminal repeats and TCR Cbeta gene indicated clonal expansion of the infected cells in 3 and 2 patients, respectively. The number of CD4+ HLA-DR+ cells appreciably increased in patients 1 (59%) and 2 (24%), who had a coronary aneurysm and central nervous system involvement, respectively. TCR gene expression examined by the inverse polymerase chain reaction methods revealed that Vbeta gene usages were preferential in all patients (Vbeta7 and Vbeta12: patient 1, Vbeta4: patient 2, Vbeta13: patients 3 and 4), compared with those in healthy controls. Valpha18 gene expression was remarkably high in patients 1 and 2. Moreover, Jbeta gene expression was skewing in the reigning Vbeta clones in all patients. Vbeta4-Jbeta1.5 and Vbeta13-Jbeta1.5 genes were clonally expressed in patients 2 and 4, respectively. These results suggest that CAEBV is associated with the restricted diversity of T-cells, which may stem from the sustained expansion of oligoclonal T-cells possibly driven by conventional viral antigens, but not, superantigens. Although the study is limited by the small number of patients, the unbalanced T-cell repertoire might contribute to the evolution of T-lymphoproliferative disease, otherwise, imply the innate defective immunity to EBV in CAEBV patients.

Generalized myositis mimicking polymyositis associated with chronic active Epstein-Barr virus infection

“…This aberrant over expression of HLA-DR has been reported to associate with failure of self-tolerance and pathogenesis of autoimmune disease [9,14]. In CAEBV, HLA-DR+ T cells increased [23]. Also in our cases, NK cells were few, and EBV infected cells did not express LMP1, as a target of cytotoxic cells.…”

“…■ Key words Epstein-Barr virus · polymyositis · myopathies · orbital · infectious diseases T or natural killer (NK) cells, which leads to the development of aggressive lymphoproliferative diseases (LPDS) [8,18,21,23,26]. CAEBV triggers or complicates many extranodal inflammatory or malignant diseases [8,18,21,23,26], but skeletal muscle involvement is rare, and polymyositis or generalized myositis like polymyositis is also rare in CAEBV.…”

“…CAEBV triggers or complicates many extranodal inflammatory or malignant diseases [8,18,21,23,26], but skeletal muscle involvement is rare, and polymyositis or generalized myositis like polymyositis is also rare in CAEBV.…”

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response

“…Four hundred and nine sequences from 19 CD8 + T lymphocyte expansions were obtained from 10 patients selected according to the main culprit drugs. Comparison of these nucleic acid sequences with those available in databases or published in the literature (15)(16)(17)(18)(19)(20)(21)(22) showed that 17 of the 19 populations of expanded CD8 + T lymphocyte contained cells with BV CDR3 sequences homologous to EBV-specific TCRs (table S4B). On average, 47% (range, 10 to 90%) of the sequences obtained from CD8 + expanded lymphocytes from DRESS patients had homology with CDR3 regions of EBV-specific CD8 + T lymphocytes (table S4A), suggesting that there is an EBV-driven selection of the CD8 + T lymphocyte response in many patients with DRESS.…”

Successful umbilical cord blood transplantation for severe chronic active Epstein‐Barr virus infection after the double failure of hematopoietic stem cell transplantation

“…Clonality of EBV-infected cells. Southern blotting was performed as previously described [15]. Briefly, 5 mg of high molecular weight DNA were digested with EcoRI and BamHI.…”