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.
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.
Larousserie
Frédérique
F
CNRS UMR 8147, Université Paris V, Institut Fédératif de Recherche Necker, Paris, France.
Bardel
Emilie
E
Pflanz
Stefan
S
Arnulf
Bertrand
B
Lome-Maldonado
Carmen
C
Hermine
Olivier
O
Brégeaud
Laurence
L
Perennec
Monique
M
Brousse
Nicole
N
Kastelein
Rob
R
Devergne
Odile
O
D015153:Blotting, Western; D017977:Deltaretrovirus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000378:metabolism*; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007378:Interleukins / Q000096:biosynthesis*; D019169:Jurkat Cells; D008223:Lymphoma / Q000378:metabolism / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism; D014412:Tumor Virus Infections / Q000378:metabolism*
D007378:Interleukins; C464565:MYDGF protein, human; D016328:NF-kappa B