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Apoptogenesis of Immunodeficiency Diseases
Leonid V. Kovalchuk1, Anatoly N. Cheredeev
1Russian State Medical University, Moscow, Russia.
The tremendous progress, which has been made in the study of cellular and molecular basis of the maturation and functioning of immune system allowed to reveal the fine pathogenetic mechanisms of many primary (genetically caused) immunodeficiencies in human. The programmed cellular death is well known to be the basic natural mechanism of positive and negative selection in T and B lymphocytes, directed to elimination of cells with defective antigen-cognitive receptors or with capacity to react against "self". The controlled apoptosis is considered to be an important mechanism for support of optimal balance in the immune system. We designate immune deficiencies, in which the enhanced (pathological) apoptosis of cells of immune system take place, as apoptotic immunodefiencies. First of all, it means the apoptosis defects in T lymphocytes and their subpopulations. Triggering signals of apoptosis are highly variable. Among them it is possible to underline the specialized signals, acting through destined for them ligands. Moreover, the parameter of apoptosis may deserve as a criterion of severity of immunodeficiency process. The enhancement of spontaneous or induced apoptosis in lymphocytes, and first of all in T lymphocytes, may be considered as a marker of apoptotic immunodeficiency. The development of antiapoptotic immunocorrective drugs is the most important goal for clinical immunology. It is quite possible that the problem may be solved on the base of cytokines (growth factors), such as interleukin-2, granulocyte-macrophage colony-stimulating factor and others.
The tremendous progress, which has been made in the study of cellular and molecular basis of the maturation and functioning of immune system allowed to reveal the fine pathogenetic mechanisms of many primary (genetically caused) immunodeficiencies in human. The programmed cellular death is well known to be the basic natural mechanism of positive and negative selection in T and B lymphocytes, directed to elimination of cells with defective antigen-cognitive receptors or with capacity to react against "self". The controlled apoptosis is considered to be an important mechanism for support of optimal balance in the immune system. We designate immune deficiencies, in which the enhanced (pathological) apoptosis of cells of immune system take place, as apoptotic immunodefiencies. First of all, it means the apoptosis defects in T lymphocytes and their subpopulations. Triggering signals of apoptosis are highly variable. Among them it is possible to underline the specialized signals, acting through destined for them ligands. Moreover, the parameter of apoptosis may deserve as a criterion of severity of immunodeficiency process. The enhancement of spontaneous or induced apoptosis in lymphocytes, and first of all in T lymphocytes, may be considered as a marker of apoptotic immunodeficiency. The development of antiapoptotic immunocorrective drugs is the most important goal for clinical immunology. It is quite possible that the problem may be solved on the base of cytokines (growth factors), such as interleukin-2, granulocyte-macrophage colony-stimulating factor and others.
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