Interleukin-10 inhibits apoptotic cell death in infectious mononucleosis T cells.
T lymphocytes from patients with acute EBV-induced infectious mononucleosis rapidly die by apoptosis in vitro. Because human and viral IL-10 are likely to be induced during acute EBV infection and display a variety of functions on human T cells, we examined IL-10 effects on infectious mononucleosis T cell death. After 12 h of incubation in medium alone, only 35.6 (+/- 8.2%) of the originally seeded infectious mononucleosis T cells were viable. Addition of human IL-10 (100 U/ml) to T cell 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 this 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. Morphology and analysis of DNA after separation on agarose gels showed that IL-10 inhibits loss of cell volume, chromatin condensation, and DNA fragmentation, characteristics of death by apoptosis. As assessed by [3H]thymidine incorporation, the T cells were not induced to proliferate by IL-10 above the level exhibited when first removed from blood. T cells protected from death by IL-10 proliferated to IL-2 and spontaneously killed sensitive targets as effectively as medium-precultured T cells. Thus, IL-10 promotes the survival of infectious mononucleosis T cells otherwise destined to die by apoptosis and may be critical for the establishment of immunologic memory after resolution of the illness.
Laboratory of Immunology, Food and Drug Administration, Rockville, Maryland 20852.
K
K
Taga
J
J
Chretien
B
B
Cherney
L
L
Diaz
M
M
Brown
G
G
Tosato
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D007244:Infectious Mononucleosis / Q000276:immunology*; D016753:Interleukin-10 / Q000494:pharmacology*; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
D016753:Interleukin-10