HUMAN INTERLEUKIN-10 EXPRESSION IN T-NATURAL-KILLER-CELL LYMPHOMAS - ASSOCIATION WITH ANAPLASTIC LARGE-CELL LYMPHOMAS AND NASAL NATURAL-KILLER-CELL LYMPHOMAS

Several cytokines have been implicated in the pathogenesis of human ly mphomas, Among them, interleukin-10 (IL-10) is a pleiotropic cytokine with various biological effects on B and T lymphocyres. Its expression has been essentially studied in B-cell lymphomas, where it appears to act as an autocrine growth factor. BCRF1 (also called viral IL-10), a n open reading frame of Epstein-Barr virus, exhibits extensive sequenc e and functional homologies with human IL-10. Some entities belonging to T- or natural killer (NK)-cell lymphomas are characterized by a fre quent association with Epstein-Barr virus. We analyzed 39 cases of per ipheral T-cell lymphoma, as well as 7 cases of nasal NK-cell lymphoma, for the presence of IL-10 transcripts by in situ hybridization, to se e whether this cytokine was expressed in these tumors and whether its expression could be related to their histological subtype and to the p resence of Epstein-Barr virus. Because the riboprobe used for in situ hybridization recognizes both human and viral IL-10, 12 cases were als o analyzed by reverse transcription-polymerase chain reaction to verif y the human or viral origin of IL-10, It was found that 8 of 11 (73%) anaplastic large cell lymphomas (ALCLs), 2 of 11 (18%) pleomorphic T-c ell lymphomas, and 5 of 7 (43%) nasal NK-cell lymphomas exhibited a la rge number of IL-10-expressing cells, whereas only rare scattered cell s were detected in angioimmunoblastic (11 of 11) and In gamma delta T- cell lymphomas (6 of 6), In ALCLs, the pattern of IL-10 mRNA-expressin g cells showed an overlapping with the CD30 staining and preferential localization in sinusal and perifollicular areas, thereby suggesting t hat IL-10-expressing cells were tumor cells. Furthermore, IL-10 transc ripts were detected in the SU-DHL-1 anaplastic lymphoma cell line. No correlation with Epstein-Barr virus profile was found, because all cas es of ALCL were negative for EBER 1 and 2 genes by in situ hybridizati on, We confirmed the presence of human IL-10 mRNA by reverse transcrip tion-polymerase chain reaction in ALCLs as well as in NK-cell lymphoma s, whereas viral IL-10 was not detected. Thus, human and not viral IL- 10 is frequently expressed by tumor cells in ALCLs and nasal NK-cell l ymphomas, In view of its function in the proliferation and the differe ntiation of cytotoxic T and MC cells, and its immunosuppressive proper ties, IL-10 may have a role in the pathogenesis of these lymphomas.