Human and viral interleukin‐10 in Hodgkin's disease, and its influence on CD4⁺ and CD8⁺ T lymphocytes

Abstract

The Epstein-Barr virus (EBV) is closely related to Hodgkin's disease (HD), while the BCRF-I (viral [v] IL-10) gene of the EBV is highly homologous to the human interleukin-10 (h IL-10) gene. To investigate the relationship of IL-10 and HD, we performed both immunostaining and in situ hybridization (ISH) in 30 cases of HD. The presence of EBV in Hodgkin (H) and Reed-Sternberg (RS) cells was seen in 16 of the 30 cases, by ISH of the EBV EBER-I region and/or immunostaining of latent membrane protein (LMP-I). Of the 16 EBV-positive cases, 12 also showed IL-10 antigen (Ag) in H and RS cells by immunostaining, 5 of the 16 demonstrated hIL-10 RNA by ISH and 14 of the 16 showed vIL-10 RNA. But only 2 of the 14 EBV-negative cases showed IL-10 Ag, and one of them showed hIL-10 RNA, while none demonstrated vIL-10 RNA. The T cells in the HD-involved tissues were found to be mainly CD4-positive T cells, and had no association with EBV infection. However, the lymphocytes surrounding H and RS cells were more frequently CD4 cells and rarely CD8 cells in the EBV-positive cases, in contrast with the EBV-negative cases. The above results indicate that an EBV infection influenced both cytokine synthesis and the response of T cells in HD.

Infiltration of Th1 and Th2 lymphocytes around Hodgkin and Reed‐Sternberg (H&RS) cells in Hodgkin disease: Relation with expression of CXC and CC chemokines on H&RS cells

“…3 We have also demonstrated previously that lymphocytes surrounding H&RS cells were more frequently CD4 ϩ cells and rarely CD8 ϩ cells in EBV-positive cases, compared to EBV-negative cases. 27 In the present study, T-lymphocytes, especially CD 4ϩ cells surrounding H&RS cells, were in direct contact with H&RS cells. In comparison, B (CD19 ϩ )-lymphocytes, CD8 ϩ T cells and CD56 ϩ NK cells comprised the minority.…”

Direct Immunosuppressive Effects of EBV-Encoded Latent Membrane Protein 1

“…We and others have previously shown that in EBV-positive cases of HD, high numbers of cells (either neoplastic or reactive cells) express IL-10, whereas low numbers of cells showed IL-2 expression (14,32,33). This is supported by in vitro data showing that LMP1 is able to up-regulate the expression of IL-10 upon transfection into LMP1-negative Burkitt's lymphoma cell lines (34).…”

Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin's disease: an independent biological prognostic marker

“…Another mechanism whereby tumor cells might escape from CTL-mediated killing is expression of interleukin IL-10, which has direct suppressive effects on CTLs, 56,57 and which has been shown to be expressed in both HD and ALCL. [58][59][60] However, this mechanism would not confer on tumor cells resistance to chemotherapy, and therefore would not explain our findings.…”