Analysis of Interleukin-27 (EBI3/p28) Expression in Epstein-Barr Virus- and Human T-Cell Leukemia Virus Type 1-Associated Lymphomas: Heterogeneous Expression of EBI3 Subunit by Tumoral Cells

• Published in: The American journal of pathology Vol. 166; no. 4; pp. 1217 - 1228
• Main Authors: Larousserie, Frederique, Bardel, Emilie, Pflanz, Stefan, Arnulf, Bertrand, Lome-Maldonado, Carmen, Hermine, Olivier, Bregeaud, Laurence, Perennec, Monique, Brousse, Nicole, Kastelein, Rob, Devergne, Odile
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.04.2005; American Society for Investigative Pathology
• Subjects: Biological and medical sciences; Blotting, Western; Deltaretrovirus - metabolism; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Infections - metabolism; Flow Cytometry; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - metabolism; Humans; Immunohistochemistry; In Situ Hybridization; Interleukins - biosynthesis; Investigative techniques, diagnostic techniques (general aspects); Jurkat Cells; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma - metabolism; Lymphoma - virology; Medical sciences; NF-kappa B - metabolism; Original Research Paper; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Tumor Virus Infections - metabolism; Gammaherpesvirinae; Deltaretrovirus; Herpesviridae; Interleukin; Cytokine; Retroviridae; Malignant hemopathy; Epstein Barr virus; Subunit; Lymphoma; Virus; Anatomic pathology; Lymphoproliferative syndrome; Tumor; HTLV-I virus; Cell
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)62340-1

Interleukin (IL)-27 is a novel heterodimeric cytokine of the IL-12 family that is composed of two subunits, Epstein-Barr virus (EBV)-induced gene 3 (EBI3) and p28. EBI3 is expressed at high levels in EBV-transformed B-cell lines and is induced in vitro by the EBV oncogene LMP1 in a nuclear factor (NF)-kappaB-dependent manner. We show here that EBI3 expression is up-regulated in human T-cell leukemia virus type 1 (HTLV-1)-infected cell lines and IL-2-dependent leukemic cells from adult T-cell leukemia/lymphoma (ATL) patients, compared to normal activated T cells. EBI3 expression was decreased in HTLV-1-transformed cells after treatment with the NF-kappaB inhibitor BAY11-7082 and was induced in Jurkat cells by expression of HTLV-1 wild-type Tax oncoprotein, but not by the Tax mutant M22, which is defective for NF-kappaB activation. In situ analysis of EBI3 and p28 expression in Hodgkin's lymphomas (HLs), in various EBV-associated lymphoproliferative disorders (LPDs) (including post-transplant LPDs and nasal-type NK/T-cell lymphomas), and in ATL showed that EBI3 was expressed by neoplastic cells in all cases of HL and of LMP1-positive EBV-associated LPD, at variable levels in ATL cases, but rarely in control T-cell lymphomas. In contrast, in all lymphomas tested, no or few tumoral cells expressed p28. Consistent with these data, no significant p28 or IL-27 expression was detected in HL-derived cell lines, or in EBV- or HTLV-1-transformed cell lines. This selective overexpression of EBI3 by transformed cells suggests that EBI3 may play a role, independently from its association to p28, in regulating anti-viral or anti-tumoral immune responses.