mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2014-5-403-408mimmun-725Research ArticleОБЗОРЫREVIEWSГОМЕОСТАТИЧЕСКАЯ ПРОЛИФЕРАЦИЯ КАК ОСНОВА НЕИЗБЕЖНОГО ФОРМИРОВАНИЯ ТОТАЛЬНОГО ИММУНОДЕФИЦИТАHOMEOSTATC PROLIFERATION AS A BASIS FOR THE INEVITABLE FORMATION OF TOTAL IMMUNODEFICIENCYКозловА. В.KozlovV. A.

д.м.н., профессор, академик РАН, директор ФГБУ «НИИ клинической иммунологии» СО РАМН 630090, Россия, г. Новосибирск, ул. Ядринцевская, 14. Тел.: 8 (383) 222-66-27. Факс: 8 (383) 222-70-28

PhD, MD, Professor, Full Member of Russian Academy of Medical Sciences, Director, Research Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences 630090, Russian Federation, Novosibirsk, Yadrintsevskaya str., 14. Phone: 7 (383) 222-66-27. Fax: 7 (383) 222-70-28.

vakoz40@yandex.ruФГБУ «НИИ клинической иммунологии» СО РАМН, г. Новосибирск, РоссияРоссияResearch Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk, Russian FederationRussian Federation201422112014165403408Copyright © Козлов А.В., 20142014Козлов А.В.Kozlov V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/725

Многочисленные литературные данные свидетельствуют о постепенном, но неуклонном снижении иммунологической реактивности организма, уменьшении его способности формировать специфический иммунный ответ как клеточного, так и гуморального типа. Результатом подобного рода изменений является увеличение частоты различного рода заболеваний, включая онкологические и аутоиммунные. В конце концов, даже в нормальном организме, без явных проявлений патологии, формируется старческий иммунодефицит, механизмы которого остаются до конца не выясненными. Ясно, по-видимому, только одно, что они многокомпонентные. Можно предположить, что одним из этих механизмов, который может стать ведущим, является процесс гомеостатической пролиферации, сопровождающий любые негативные влияния на численность лимфоцитов в организме и проявляющийся уменьшением способности лимфоцитов узнавать чужеродные антигены на фоне увеличения аутореактивных клеток.

Numerous literature data indicate to gradual, but steady ageependent decrease of immunological reactivity in human organism, manifesting as a reduced ability to develop specific immune response, both of cellular and humoral type. Such negative trends result into increased proposition and frequency of various diseases, including cancer and autoimmune disorders. Finally, an age-associated immunodeficiency is developed even in normal organism, without clear background of specific disorders. The multicomponent mechanisms of such deficiency are not yet fully clarified. One may assume that, among these potentially leading mechanisms, a homeostatic proliferation may be of sufficient importance. This type of cell growth is shown to accompany any negative effects on the numbers of lymphocytes in the body. It manifests as a reduced ability of lymphocytes to recognize foreign antigens associated with a background increase of self-reactive cells.

гомеостатическая пролиферацияиммунодефицитнаивные Т-клеткиТ-клетки памятиапоптозhomeostatic proliferationimmunodeficiencyna ve T cellsmemory T cellsapoptosisReferencesКозлов В.А. Свободная внеклеточная ДНК в норме и при патологии // Медицинская иммунология. 2013. Т. 15, № 5. С. 399-412. [Kozlov V.A. Svobodnaya vnekletochnaya DNK v norme i pri patologii [Free, extracellular dna in norm and pathology]. Meditsinskaya immunologiya = Medical Immunology, 2013, Vol. 15, no. 5, pp. 399-412].Козлов В.А. Свободная внеклеточная ДНК в норме и при патологии // Медицинская иммунология. 2013. Т. 15, № 5. С. 399-412. [Kozlov V.A. Svobodnaya vnekletochnaya DNK v norme i pri patologii [Free, extracellular dna in norm and pathology]. Meditsinskaya immunologiya = Medical Immunology, 2013, Vol. 15, no. 5, pp. 399-412].Heninger A.K., Theil A., Petzold C., Huebel N., Kretschmer K., Bonifacio E., Monti P. IL-7 abrogatesHeninger A.K., Theil A., Petzold C., Huebel N., Kretschmer K., Bonifacio E., Monti P. IL-7 abrogatessuppressive activity of human CD4+CD25+FoxP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells. J. Immunol., 2012, Vol. 189, no. 12, pp. 5649-5658.suppressive activity of human CD4+CD25+FoxP3+ regulatory T cells and allows expansion of alloreactive and autoreactive T cells. J. Immunol., 2012, Vol. 189, no. 12, pp. 5649-5658.Hickman P.S., Turka L.A. Homeostatic T cell proliferation as a barrier to T cell tolerance. Philos Trens R Soc Lond B Biol Sci., 2005, Vol. 360, no. 1461, pp. 1713-1721.Hickman P.S., Turka L.A. Homeostatic T cell proliferation as a barrier to T cell tolerance. Philos Trens R Soc Lond B Biol Sci., 2005, Vol. 360, no. 1461, pp. 1713-1721.Kieper W.C., Burghardt J.T., Surt C.D. A role for TCR affinity in regulating na ve T cell homeostasis. J. Immunol., 2004, Vol. 172, no. 1, pp. 40-44.Kieper W.C., Burghardt J.T., Surt C.D. A role for TCR affinity in regulating na ve T cell homeostasis. J. Immunol., 2004, Vol. 172, no. 1, pp. 40-44.Kimmig S., Przybylski G.K., Schmidt C.A., Laurisch K., M wes B., Radbruch A., Thiel A. Two subset of naive helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med., 2002, Vol. 195, no. 6, pp. 789-794.Kimmig S., Przybylski G.K., Schmidt C.A., Laurisch K., M wes B., Radbruch A., Thiel A. Two subset of naive helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J. Exp. Med., 2002, Vol. 195, no. 6, pp. 789-794.Koetz K., Bryl E., Spickschen K., O’Fallon W.M., Goronzy J.J., Weyand C.M. T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci USA, 2000, Vol. 97, no. 16, pp. 9203-9208.Koetz K., Bryl E., Spickschen K., O’Fallon W.M., Goronzy J.J., Weyand C.M. T cell homeostasis in patients with rheumatoid arthritis. Proc Natl Acad Sci USA, 2000, Vol. 97, no. 16, pp. 9203-9208.Lario M., Munoz L., Ubeda M., Borrero M.-J., Martinez J. Defective thymopoiesis and poor peripheral homeostatic replenish-ment of T-helper cells cause T-cell lymphopenia in cirrhosis. J. Hepatology, 2013, Vol. 59, pp. 723-730.Lario M., Munoz L., Ubeda M., Borrero M.-J., Martinez J. Defective thymopoiesis and poor peripheral homeostatic replenish-ment of T-helper cells cause T-cell lymphopenia in cirrhosis. J. Hepatology, 2013, Vol. 59, pp. 723-730.Liu Y., Lai L., Chen Q., Song Y., Xu S., Ma F., Wang X., Wang J., Yu H., Cao X., Wang Q. MicroRNA-494 is required for the accumulation and function of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J. Immunol., 2012, Vol. 188, pp. 5500-5510.Liu Y., Lai L., Chen Q., Song Y., Xu S., Ma F., Wang X., Wang J., Yu H., Cao X., Wang Q. MicroRNA-494 is required for the accumulation and function of tumor-expanded myeloid-derived suppressor cells via targeting of PTEN. J. Immunol., 2012, Vol. 188, pp. 5500-5510.Nesic D., Vukmanoviċ S. MHC class I is required for peripheral accumulation of CD8+ thymic emigrants. J. Immunol., 1998, Vol. 160, no. 8, pp. 3705-3712.Nesic D., Vukmanoviċ S. MHC class I is required for peripheral accumulation of CD8+ thymic emigrants. J. Immunol., 1998, Vol. 160, no. 8, pp. 3705-3712.Provinciali M., Moresi R., Donnini A., Lisa R.M. Reference values for CD4+ and CD8+ T lymphocytes with naïve or memory phenotype and their association with mortality in the elderly. Gerontology, 2009, Vol. 55, pp. 314-321.Provinciali M., Moresi R., Donnini A., Lisa R.M. Reference values for CD4+ and CD8+ T lymphocytes with naïve or memory phenotype and their association with mortality in the elderly. Gerontology, 2009, Vol. 55, pp. 314-321.Sport s C., Hakim F.T., Memon S.A., Zhang H., Chua K.S., Brown M.R., Fleisher T.A., Krumlauf M.C., Babb R.R., Chow C.K., Fry T.J., Engels J., Buffet R., Morre M., Amato R.J., Venzon D.J., Korngold R., Pecora A., Gress R.E., Mackall C.L. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of na ve T cell subsets. J. Exp. Med., 2008, Vol. 205, no. 7, pp. 1701-1714.Sport s C., Hakim F.T., Memon S.A., Zhang H., Chua K.S., Brown M.R., Fleisher T.A., Krumlauf M.C., Babb R.R., Chow C.K., Fry T.J., Engels J., Buffet R., Morre M., Amato R.J., Venzon D.J., Korngold R., Pecora A., Gress R.E., Mackall C.L. Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of na ve T cell subsets. J. Exp. Med., 2008, Vol. 205, no. 7, pp. 1701-1714.Takeda S., Rodewald H.R., Arakawa H., Bluethmann H., Shimizu T. MHC class II molecules are not required for survival of newly generated CD4+ T cell, but affect their long0term life span. Immunity, 1996, Vol. 5, no. 3, pp. 217-228.Takeda S., Rodewald H.R., Arakawa H., Bluethmann H., Shimizu T. MHC class II molecules are not required for survival of newly generated CD4+ T cell, but affect their long0term life span. Immunity, 1996, Vol. 5, no. 3, pp. 217-228.Van Belle T.L., Dooms H., Boonefaes T., Wei X.Q., Leclercq G., Grooten J. IL-15 augments TCR-induced CD4+ T cell expansion in vitro by in-habiting the suppressive function of CD25 high CD4+ T cells. PLoS One, 2012, Vol. 7, no. 9, e45299.doi:10.1371.Van Belle T.L., Dooms H., Boonefaes T., Wei X.Q., Leclercq G., Grooten J. IL-15 augments TCR-induced CD4+ T cell expansion in vitro by in-habiting the suppressive function of CD25 high CD4+ T cells. PLoS One, 2012, Vol. 7, no. 9, e45299.doi:10.1371.Weng N.P. Telomere and adaptive immunity. Mech Ageing Dev., 2008, Vol. 129, pp. 60-66.Weng N.P. Telomere and adaptive immunity. Mech Ageing Dev., 2008, Vol. 129, pp. 60-66.Wrzesinski S.H., Wan Y.Y., Flavell R.A. Transforming growth factor-β and immune response: implication for anticancer therapy. Clin Cancer Res., 2007, Vol. 13, no. 18, pp. 5262-5270.Wrzesinski S.H., Wan Y.Y., Flavell R.A. Transforming growth factor-β and immune response: implication for anticancer therapy. Clin Cancer Res., 2007, Vol. 13, no. 18, pp. 5262-5270.

The authors declare that there are no conflicts of interest present.