Background: Hodgkin’s lymphoma (HL) is characterized by a minority of neoplastic cells, the so-called Reed-Sternberg (RS) cells, and an admixture of reactive cells including lymphocytes, plasma cells, eosinophils and histiocytes. Cytokines produced in HL, either by RS or infiltrating cells, might explain the presence and maintenance of an impaired immune response, Chemokines (cytokines with chemoattractant properties) produced by RS cells play a major role in leukocyte trafficking. These molecules with specific receptor affinities contribute, for example by attracting TH2-like T cells, to the maintenance of a favorable environment...

Reed-Sternberg (RS) cells, the neoplastic cells of Hodgkin lymphoma (HL) have clonal immunoglobulin gene rearrangements. The presence of somatic mutations suggests a germinal center origin, whereas the presence of crippling mutations suggests rescue of RS precursors from apoptosis by a transforming event. Epstein-Barr virus (EBV), which can be detected in 30-50% of HL cases, probably plays a role in this transforming event. The frequent presence of p53 protein expression in RS cells also suggests a role of the TP53 gene in this escape from apoptosis. Although mutations of...

Recent studies provide evidence that Reed-Sternberg (R-S) cells produce factors that may explain the characteristic inflammatory infiltrate in the affected tissues of Hodgkin lymphoma. The various chemokines and cytokines that are produced lead to a preferential influx of Th2-type T cells and suppress Th1-type immune responses. Overall, the immunophenotype of the lymphocytes surrounding the R-S cells is consistent with anergic and/or Th2-type T cells. Therefore, these cells do not support a cytotoxic anti-tumor response. Since the R-S cells are neoplastic B cells, the cytokines produced by these T...

Epstein-Barr virus (EBV) is present in Reed-Sternberg (RS) cells of a substantial proportion of Hodgkin’s lymphoma cases. Most EBV-positive cases are also MHC class I-positive, whereas the majority of EBV-negative cases lack detectable levels of MHC class I expression. Application of the SAGE technique has led to the identification of tags corresponding to MHC class I and beta(2)-microglobulin genes in the EBV- and MHC class I-negative L428 Hodgkin’s cell line. Further expression studies indicated that single RS cells that do not express HLA class I also lack beta(2)-microglobulins...

In a pilot study on SAGE on Reed-Sternberg cells we have sequenced 1055 tags representing 701 genes. Screening of the GenBank database resulted in the identification of a corresponding gene or EST for 490 of them. For 211 of the tags no homology could be detected. A major problem of the serial analysis of gene expression (SAGE) approach is how to further analyse the unknown tags. We have developed an RT-PCR-based method, rapid analysis of unknown SAGE tags (RAST-PCR), to analyse the expression of the corresponding genes. This...