Frequent expression of the Epstein-Barr virus (EBV)-induced gene, EBI3, an IL-12 p40-related cytokine, in Hodgkin and Reed-Sternberg cells

J Pathol. 2002 Nov;198(3):310-6. doi: 10.1002/path.1217.

Abstract

Epstein-Barr virus (EBV)-associated Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) usually occur in patients without clinically manifest deficiencies in anti-viral immunity. In spite of expressing viral proteins, both tumours are apparently able to escape EBV-specific immunity in vivo. EBI3 is an EBV-induced cytokine homologous to the interleukin (IL)-12 p40 subunit and can heterodimerize with IL-12 p35. It has been suggested that EBI3 may function to antagonize IL-12 and to inhibit the development of a Th1 immune response. EBI3 expression has been studied in tumour entities frequently associated with EBV infection to examine if EBI3 might contribute to local modulation of the immune response. It is shown that EBI3 is strongly expressed in Hodgkin and Reed-Sternberg cells in 32 of 33 HL cases, independently of the EBV status of the tumour cells. Furthermore, EBI3 expression was detected in the epithelial tumour cells of six of 40 NPC biopsies but not in Burkitt lymphomas. The results suggest that EBI3 may be an additional component of the repertoire employed by Hodgkin and Reed-Sternberg cells to inhibit an effective anti-tumour or anti-viral immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Burkitt Lymphoma / immunology
  • Burkitt Lymphoma / metabolism
  • Burkitt Lymphoma / virology
  • Epstein-Barr Virus Infections / complications*
  • Glycoproteins / metabolism*
  • Herpesvirus 4, Human / isolation & purification
  • Hodgkin Disease / immunology
  • Hodgkin Disease / metabolism*
  • Hodgkin Disease / virology
  • Humans
  • Interleukin-12 / metabolism
  • Interleukin-12 Subunit p35
  • Interleukins
  • Minor Histocompatibility Antigens
  • Nasopharyngeal Neoplasms / immunology
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Proteins / metabolism*
  • Protein Subunits / metabolism
  • Receptors, Cytokine*
  • Reed-Sternberg Cells / metabolism*
  • Tumor Cells, Cultured

Substances

  • EBI3 protein, human
  • Glycoproteins
  • IL12A protein, human
  • Interleukin-12 Subunit p35
  • Interleukins
  • Minor Histocompatibility Antigens
  • Neoplasm Proteins
  • Protein Subunits
  • Receptors, Cytokine
  • Interleukin-12