Interleukin-10 dose-dependent regulation of CD4+ and CD8+ T cell- mediated graft-versus-host disease

Bruce R. Blazar, Patricia A. Taylor, Angela Panoskaltsis-Mortari, Satwant K. Narula, Sidney R. Smith, Maria G. Roncarolo, Daniel A. Vallera

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Background. Endogenous interleukin (IL)-10 production has been associated with the lack of graft-versus-host disease (GVHD) in human recipients of MHC-disparate donor grafts. Paradoxically, we have shown that the exogenous administration of high doses (30 μg/dose) of IL-10 to murine recipients of MHC-disparate grafts accelerates GVHD lethality. Methods. The effects of IL-10 on GVHD mediated by either CD4+ or CD8+ T cells was examined in studies involving exogenous IL-10 administration or the infusion of T cells from IL-10-deficient (-/-) donor mice. The role of interferon (IFN)-γ on IL-10-induced GVHD acceleration was studied using IFN-γ- deficient (-/-) donor mice or neutralizing monoclonal antibody. Results. IL- 10 was found to have a dose-dependent effect on the GVHD lethality mediated by either CD4+ or CD8+ T cells. High doses of exogenous IL-10 accelerated GVHD lethality. IFN-γ release was not responsible for the IL-10 facilitation of GVHD lethality. Paradoxically, low doses of IL-10 protected mice against GVHD lethality. The GVHD protective effect of the bioavailability of small amounts of IL-10 was confirmed by demonstrating that the infusion of T cells from IL-10 -/- donors accelerated GVHD lethality. Conclusions. The results suggest that IL-10 has a dose-dependent effect on the GVHD lethality mediated by CD4+ or CD8+ T cells, such that high doses accelerate lethality, while low amounts of bioavailable IL-10 are protective.

Original languageEnglish (US)
Pages (from-to)1220-1229
Number of pages10
JournalTransplantation
Volume66
Issue number9
DOIs
StatePublished - Nov 15 1998

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