Interleukin-10 (IL-10) was originally identified as a cytokine produced by mouse TH2 cells that inhibits interferon production by TH1 cells. Recently, human IL- 10 has been sequenced and found to have approximately 70% homology with the BCRF-1 open reading frame of Epstein-Barr virus. Similar to mouse IL-10, human IL-10 has been found to inhibit interferon production by human T cells, a property shared by the protein encoded by BCRF-1. The purpose of our investigation was to assess a possible role for IL-10 and BCRF-1 in the control of EBV infection. In initial experiments we have demonstrated that both human IL-10 as well as BCRF-1 protein are potent inhibitors of mitogen-induced T cell proliferation. This inhibitory effect is associated with inhibited IL-2 production and is reversed by addition of exogenous IL-2 to the suppressed cultures. Confirming previous observations, we also found that IL-10 and BCRF-1 protein inhibit Interferon production. This effect, however, appears to be independent of the growth inhibitory functions of IL-10 and BCRF-1. In a subsequent set of experiments, we have examined whether IL-10 inhibition of T cell growth occurs through a direct effect on T cells or rather occurs indirectly acting upon a different cell type. Using purified T cells and a tetanous toxoid- specific T cell clone activated by immobilized OKT3, we found that IL-10 can act directly on the T cell. This finding is novel because previous data on this subject have strongly suggested that IL-10 does not affect T cells directly but always through the monocyte. Recently, we have examined the effects of IL-10 on T cell death occurring after IL-2 deprivation in IL-2 dependent T cells and in T cells from patients with infectious mononucleosis. Although we expected IL-10 to promore T cell death, we instead found that this cytokine protects T cells from death by apoptosis in both systems. Thus, in addition to inhibiting T cell growth, IL-10 can prevent or delay programmed cell death. In related studies, we measured levels of human IL-10 and EBV-derived IL-10 during the course of EBV-induced infectious mononucleosis. We found that both human and viral IL-10 are abnormally elevated in the serum of patients with acure EBV-induced infectious mononucleosis, but not in saliva. Thus, the role of IL-10 and viral IL- 10 during primary EBV infection is complex, and it is not completely clear whether the cytokine serves best the interests of virus infecting his host or whether those of the host infected with the virus.
