Interleukin-10 (IL-10) was originally identified as a cytokine produced by mouse TH2 cells that inhibits interferon production by TH1 cells. Subsequently, human IL-10 was sequenced and found to have approximately 70% homology with BCRF-1, an open reading frame in the Epstein-Barr virus (EBV) genome. Similar to mouse and human IL-10, we and others found that the BCRF-1 protein inhibits T cell proliferation and interferon production by human T cells. The purpose of our investigation was to assess a possible role for IL-10 and BCRF-1 in the control of EBV infection. Because EBV, during evolution, has captured the IL-10 cytokine gene, it was hypothesized that this might be useful for virus survival and spread. Thus, IL-10 may be of importance in the pathogenesis of EBV-associated illnesses. In a set of recent experiments, we have examined the effects of IL-10 on programmed cell death (apoptosis) occurring in normal IL-2 dependent T cells after IL-2 deprivation and in T cells from patients with acute EBV-induced infectious mononucleosis. Our expectation was that IL-10 to promoted T cell death, but instead we found that this cytokine protects T cells from death by apoptosis in both systems. Importantly, T cells protected from death by IL-10 or BCRF-1 are functional, as they can proliferate and exert cytotoxic functions. 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 acute 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 clear whether the cytokine serves best the interests of virus infecting his host or those of the host infected with the virus. Taga, K., Cherney B., and Tosato G. IL-10 inhibits apoptotic cell death in human T cells starved of IL-2. Int. Immunol 4:1599-1608, 1994 Saville, M.W., Taga K., Foli A., Broder S., Tosato G., and Yarchoan R. Effects of Interleukin 10 on in vitro HIV-1 replication. Blood 83: 3591-99, 1994 Taga K., Chretien J., Cherney B., Diaz L., Brown,M., and Tosato G. Il-10 inhibits apoptotic cell death in infectious mononucleosis T cells J. Clin. Invest. 94: 251-260, 1994 Taga H., Taga K., Wang F., Chretien J., and Tosato G. Human and viral Interleukin 10 in acute Epstein-Barr virus-induced Infectious Mononucleosis. J. Infect. Dis. 171: 1347-50, 1995.
