IL-10 inhibits apoptotic cell death in human T cells starved of IL-2.
IL-10 was originally described as an inhibitory factor produced by murine Th2 lymphocytes that suppresses IFN-gamma production by activated murine Th1 lymphocytes. In this study, we have analyzed the effect of human IL-10 on human T cell death induced by IL-2 deprivation. IL-2-dependent T lymphocytes rapidly die when deprived of IL-2. This cell death was found to involve loss of cell volume, chromatin condensation, and DNA fragmentation, all characteristic of apoptosis. After 2 days incubation in culture medium without IL-2, the viability of TM11 cells (a tetanus toxoid-specific T cell line) and of activated peripheral blood T cells decreased from > 98% to 34.3 (+/- 2.9) and 39.7 (+/- 5.5%) respectively. Addition of purified human IL-10 (100 U/ml) to these IL-2-starved cells significantly improved cell viability (66.0 +/- 6.0 and 73.1 +/- 12.3% respectively, P = 0.0051). This protective effect of IL-10 was dose-dependent and was neutralized by the anti-human IL-10 mAb 19F1. It was neither accompanied by T cell growth stimulation as judged by [3H]thymidine incorporation nor neutralized by anti-IL-2 or anti-IL-2 receptor (CD25) antibodies. Analysis of DNA after separation on agarose gels revealed that IL-10 inhibits DNA fragmentation in IL-2-starved T cells. T cells protected from death by IL-10 were indistinguishable from IL-10-untreated viable T cells in the ability to proliferate in response to IL-2. Thus, another property of IL-10 is to promote the survival of IL-2-dependent T cells otherwise destined to die by apoptosis.
Taga
K
K
Laboratory of Immunology, Center for Biologics Evaluation and Research, Bethesda, MD 20892.
Cherney
B
B
Tosato
G
G
D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D004587:Electrophoresis, Agar Gel; D005455:Fluorescent Antibody Technique; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D007376:Interleukin-2 / Q000172:deficiency / Q000502:physiology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D016753:Interleukin-10