Genetic resistance to bone marrow transplantation

The homeostasis of several tissues is maintained by a process of proliferation and differentiation to replace the cells which are constantly lost. The most undifferentiated cells of a certain tissue, capable of proliferation and differentiation, are stern cells. Stem cells have "the capacity for extensive proliferation, resulting in renewal of its own kind as well as giving rise to fully differentiated cells" (Caffrey-Tyler and Everett, 1966). In multicellular animals various types of stem cells can exist in a more or less differentiated form. In the most primitive multicellular organisms, the parazoa, any cell type is capable of proliferation and differentiation into the different cell types which form the organism. In these organisms each cell can be considered as a stem cell. Among higher classified animals, Planarians (Platyhelminthes) are known for their enormous capacity to regenerate. These flatworms carry an omnipotent stem cell called neoblast. Different techniques were used to prove that neoblast population forms a stem cell pool which can differentiate into any cell type of the animal in case of a spontaneous fissure of the animal or a healing process after a trauma (cf. BrQ\ndsted, 1969). Recent radiobiological studies produced suggestive evidence that the survival of planarians after irradiation is dependent on the presence of one single cell population (Lange, 1968a, b). This evidence is in favour of the neoblast concept, but could also be in favour of the concept which attributes the regeneration to dedifferentiation of differentiated cells. In vertebrates various types of stem cells have been found. Cell renewal systems in these animals are generaUy restricted to tissues with relatively short living cells. Cell renewal systems are also found in other tissues and have a function in repair of local injuries. This latter type of repair seldom results in remodeling of the original form of the injured tissue. Among the vertebrates only the Urodele amphibians (Caudata) show a .complete regeneration of an injured or amputated limb or taiL Most authors assume that this regeneration is not dependent on stem cells1 but on dedifferentiation of differentiated cells (cf. de Both, 1969). The most active cell renewal systems are those which produce ceHs, that have a relatively short life time when compared with the life span of the individual. Examples of these cell renewal systems are among others the hemopoietic system, the epithelia of the skin, the gastro-intestinal tract and the urogenital system

Mobilization of haemopoietic stem cells (cfu) into the peripheral blood of the mouse; effects of endotoxin and other compounds

Factors affecting the circulation of haemopoietic stem cells (CFU) in the peripheral blood of mice were investigated. I.v. injection of sublethal doses of endotoxin, trypsin and proteinase appeared to raise the number of CFU per ml blood from about 30–40 to about 300–400 or more within 10 min. The effect was smaller when smaller doses of the substances were injected. After this initial rise the number of circulating cells returned to normal in a few hours. Following endotoxin there was a second rise which started 2–3 days after injection and attained a peak on the 6th–7th day. The first rise is explained as a mobilization of stem cells from their normal microenvironments into the blood stream; the second rise is considered to reflect proliferation of CFUs in the haemopoietic tissues. The spleen seems to be acting as an organ capturing CFUs from the blood and not as a source adding stem cells to the blood. The early mobilization of CFU after endotoxin injection did not coincide with a mobilization of neutrophils. The number of circulating band cells was increased during the first hours. The importance of ‘open sites’in the haemopoietic tissue for capturing CFUs was studied by emptying these sites through a lethal X‐irradiation and injecting normal bone marrow cells. When a greater number of syngeneic bone marrow cells was injected intravenously, the level of circulating CFU in irradiated mice was slightly lower than the level in unirradiated mice during the first hours. Copyrigh

Involvement of T cells in enhanced resistance to Klebsiella pneumoniae septicemia in mice treated with liposome-encapsulated muramyl tripeptide phosphatidylethanolamine or gamma interferon

We have previously shown that prophylactic administration of the liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidylethanolamine (MTPPE) and gamma interferon (IFN-gamma) results in strongly increased survival of mice from a normally lethal septicemia with Klebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various infections. In the present study, we provide evidence for a key role for T cells in host defense potentiation by the liposomal immunomodulators toward K. pneumoniae septicemia. It is shown that both CD4 and CD8 cells are important in immunomodulation, most likely due to production of IFN-gamma. Depletion of circulating IFN-gamma resulted in strong reduction of the antimicrobial host defense activation. Administration of interleukin-10 resulted in decreased antimicrobial host defense activation by liposomal immunomodulators. Moreover, administration of liposomal immunomodulators was shown to induce predominantly T-helper type 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-gamma favors Th1 and NK cell activation