Necessity of immune recognition and control of a human organ stem cell circulating in blood as a monocyte, in order to avoid some proliferating diseases.
aEcole Nationale Vétérinaire d'Alfort, France, bLaboratoire de Chimie Physique Biologiques et Médicales, ENVA, France, cLaboratoire Audiovisuel, INSERM, Le Vésinet, France
AIM: Study of the regulation of an organ stem cell present in blood. Dyregulation of stem cells has been reported to contribute to neoplasia. Organ stem cells present in blood might represent one single population of pluripotent stem cells in homeostatic equilibrium with the reserve stem cells present in the different organs. These circulating organ stem cells are normally almost quiescent. Under precise circumstances such as wound healing they may proliferate and migrate in order to participate in the regeneration of the damaged tissue. Indeed such a powerful cell has to be tightly controlled. METHODS: The organ stem cells are characterized by immunofluorescence and their killing by phagic T lymphocytes is studied by time-lapse videomicroscopy. RESULTS: Organ stem cells circulate under the appearance of monocytes. However, spontaneous expression of neural markers, including nestin, suggests a neural crest origin. Time-lapse videomicroscopy shows how a subpopulation of CD4+ T lymphocytes, called phagic T lymphocytes, destroy the organ stem cells as soon as they start differentiating in vitro. These stem cells that constitutively express HLA-DR molecules are both the activators and the targets of phagic T lymphocytes that penetrate and circulate inside them until the stem cells explode. This mode of killing is therefore different from necrosis and apoptosis. It is a beneficial exception to self tolerance, restricted to normal organ stem cells, in order to avoid their accumulation out of a repair purpose. In disorders such as fibrosis and chondrosarcoma, these circulating organ stem cells proliferate indefinitely, escape destruction by phagic T lymphocytes and as a result accumulate, giving rise to a tissue that evokes the lesion of the patient. This process observed in vitro may mimick what happens in vivo at the capillary-tissue interface. CONCLUSIONS. Failure in the regulation of circulating organ stem cells might be involved in the common early steps leading to fibrosis and some malignancies. On the opposite, excessive activation of phagic T lymphocytes might be involved in autoimmune disease. Any attempt to stop the proliferation of the organ stem cells at the capillary-tissue interface and to activate phagic T lymphocytes might be beneficial in terms of cancer prevention.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 1091 (Immunobiology).