How functional are human immune cells developed in mice? (P4376)

Abstract

After transplantation with human umbilical cord blood cells NOD-SCID IL2Rγ(null) rodents develop an human immune system which is characterized by the presence of B cells, T cells, monocytes, granulocytes and dendritic cells. The extent of the several subpopulations differs during the time after transplantation. A clear development of the immune system can be seen from immature immune system which contains mainly B cells, a few T cells in peripheral blood, during a transitional state with an additional existence of monocytes, granulocytes and denritic cells in bone marrow and spleen of the mice to a state which reminds of Graft-versus-Host-Disease. This development can be observed during a period of 10 to 20 weeks after transplantation. The B cells are able to produce high amounts of IgM in the early state and few IgG. The antigen presenting cells in the transitional state are able to express activation molecules like HLA-DR and CD86 after the injection of LPS as an immune modifying stimulus. Moreover the cells are able to produce human TNFα, IL-10, IL-1b, IFNγ and high amounts of IL-6 after stimulation with LPS in every state. Release of murine TNFα, IL10, IL-6, MCP and IL-12 was detected as well. The presence of human and murine PTX3 was also measureable after in vivo stimulation with LPS. Depending on the time point after transplantation the human immune cells are able to produce human cytokines and to express several activation markers after immune modifying stimulus.