INTERLEUKIN-10 DOSE-DEPENDENT REGULATION OF CD4+ AND CD8+ T CELL-MEDIATED GRAFT-VERSUS-HOST DISEASE1
BR Blazar, PA Taylor, A Panoskaltsis-Mortari… - …, 1998 - journals.lww.com
BR Blazar, PA Taylor, A Panoskaltsis-Mortari, SK Narula, SR Smith, MG Roncarolo…
Transplantation, 1998•journals.lww.comBackground. 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 …
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 …
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.
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