INTERLEUKIN-10 INHIBITS APOPTOTIC CELL-DEATH IN INFECTIOUS-MONONUCLEOSIS T-CELLS

T lymphocytes from patients with acute EBV-induced infectious mononucl eosis rapidly die by apoptosis in vitro. Because human and viral IL-10 are likely to be induced during acute EBV infection and display a var iety of functions on human T cells, we examined IL-10 effects on infec tious mononucleosis T cell death. After 12 h of incubation in medium a lone, only 35.6 (+/-8.2%) of the originally seeded infectious mononucl eosis T cells were viable. Addition of human IL-10 (100 U/ml) to T cel l cultures significantly improved recovery of viable cells (71.3+/-6.2 %, P = 0.0156). Viral IL-10 had comparable effects to human IL-10 in t his system. Protection from death by human and viral IL-10 (100 U/ml) was dose dependent and continued over a 6-d culture period. The human IL-10 effect was neutralized by the anti-human IL-10 mAb 19F1. Morphol ogy and analysis of DNA after separation on agarose gels showed that I L-10 inhibits loss of cell volume, chromatin condensation, and DNA fra gmentation, characteristics of death by apoptosis. As assessed by [H-3 ]thymidine incorporation, the T cells were not induced to proliferate by IL-10 above the level exhibited when first removed from blood. T ce lls protected from death by IL-10 proliferated to IL-2 and spontaneous ly killed sensitive targets as effectively as medium-precultured T cel ls. Thus, IL-10 promotes the survival of infectious mononucleosis T ce lls otherwise destined to die by apoptosis and may be critical for the establishment of immunologic memory after resolution of the illness.