Preview

Ateroscleroz

Advanced search

The suppressor cells – the basis of immunopathogenesis of atherosclerosis

Abstract

   Atherosclerosis is a vascular disease, in the formation of which is attended immunocompetent cells (macrophages, dendritic cells, lymphocytes), endothelial and smooth muscle cell elements in interaction with the lipoprotein enriched with cholesterol. Thus, circulating CD4+ T lymphocytes are differentiated mainly in Th1 cells that respond to specific antigens, such as oxidized LDL and heat shock proteins (HSP60/65) induces the processes of endothelial damage and smooth muscle cells). The question that will or will not develop atherosclerosis depends on balanced participation in the process regulatory cells with suppressor activity, in particular CD4+CD25+Foxp3+ Treg. Numerous data suggest about the reduction of Treg in patients with atherosclerosis and reducing their suppressor activity. All therapeutic effects of stimulating the activity of Treg positively influence the course of experimental atherosclerosis.

About the Author

V. A. Kozlov
Scientific Research Institute of Fundamental and Clinical Immunology
Russian Federation

630099

Yadrintsevskaya str., 14

Novosibirsk



References

1. Zhou X., Nicolleti A., Elhage R., Hansson G. K. Transfer of CD4+ T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice // Circulation. 2000. Vol. 102. P. 2919–2922.

2. Getz G. S. Immune function in atherogenesis // J. Lipid Res. 2005. Vol. 46. P. 1–10.

3. Gratz I. K., Campbell D. J. Organ-specific and memory Treg cells: specificity, development, function, and maintenance // Front. Immunol. 2014. Vol. 5. P. 1–17.

4. Wing K., Fehervari Z., Sakaguchi S. Emerging possibilities in the development and function of regulatory T cells // Internat. Immunol. 2006. Vol. 18. P. 991–1000.

5. Nilsson J., Wigren M., Shah P. K. Regulatory T cells and the control of modified lipoprotein autoimmunity-driven atherosclerosis // Trends Cardiovacs. Med. 2009. Vol. 19. P. 272–276.

6. Цырлова И. Г. Влияние клеток «эритропоэтической» селезенки на пролиферацию Т- и В-лимфоцитов / И. Г. Цырлова, Н. В. Кашлакова, В. А. Козлов // Иммунология. – 1986. – № 4. – C. 27–29.

7. Jones S., Horwood N., Cope A., Dazzi F. The antiproliferative effect of mesenchymal stem cells is a fundamental property shared by all stromal cells // J. Immunol. 2007. Vol. 179. P. 2824–2831.

8. Haniffa M. A., wang X.-N., Holtick U., Rae M., Isaacs J. D., Dickinson A. M., Hilkens C. M. U., Collin M. P. Adult Human Fibroblasts Are Potent Immunoregulatory Cells and Functionally Equivalent to Mesenchymal Stem Cells // J. Immunol. 2007. Vol. 179. P. 1595–1604.

9. Fan H., Zhao G, Liu L., Liu F., Gong W., Liu X., Yang L., Wang J., Hou Y. Pre-treatment with IL-1b enhances the efficacy of MSC transplantation in DSS-induced colitis // Cell. & Mol. Immunol. 2012. Vol. 9. P. 473–481

10. Chan J. L., Tang K. C., Patel A. P., Bonilla L. M., Pierobon N., Ponzo N. M., Rameshwar P. Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-γ // Blood. 2006. Vol. 107. P. 4817–4824.

11. Ait-Oufella H., Salomon B. L., Potteaux S., Robertson A.-K. Gourdy P., Zoll J., Merval R., Esposito B., Cohen J. L., Fisson S., Flavell R. A., Hansson G. K., Klatzmann D., Tedgui A., Mallat Z. Natural regulatory T cells control the development of atherosclerosis in mice // Nat. Med. 2006. Vol. 12. P. 178–180.

12. Taleb S., Tedgui A., Mallat Z. Regulatory T-cell immunity and its relevance to atherosclerosis // J. Int. Med. 2008. Vol. 263. P. 489–499.

13. Mor A., Planer D., Luboshits G., Afek A., Metzger S., Chajek-Shaul T., Keren G., George J. Role of naturally occurring CD4+CD25+ regulatory T cells in experimental atherosclerosis // Arterioscler. Thomb. Vasс. Biol. 2007. Vol. 27. P. 893–900.

14. McLaren J. E., Ramji D. P. Interferon gamma: a master regulator of atherosclerosis // Cytokine Growth Factor Rev. 2009. Vol. 20, N 2. P. 125–135.

15. Merzrich J. D., Fechner L. H., Zhang X., Johnson B. P., Burlingham W. J., Bradfield C. A. An interaction between kynurenine and the Aryl hydrocarbon receptor can generate regulatory T cells // Immunol. 2010. Vol. 185. P. 3190–3198.

16. De Boer O. J., van der Meer J. J., Teeling P., van der Loos C. M., van der wal A. C. Low numbers of Foxp3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions // PLos ONE. 2007. Vol. 8. e779.

17. Mor A., Luboshits G., Planer D., Keren G., George J. Altered status of CD4+CD25+ regulatory T cells in patients with acute coronary syndromes // Eur. Heart J. 2006. Vol. 27. P. 2530–2537.

18. Han S. F., Liu P., Zhang W., Bu L., Shen M., Li H., Fan Yh., Cheng K., Cheng Hx., Li Cx., Jia Gl. The opposite-direction modulation of CD4+CD25+ Treg and T helper 1 cells in acute coronary syndromes // Clin. Immunol. 2007. Vol. 124. P. 90–99.

19. Gandhi R., Farez M. F., wang Y., Kozoriz D., Quintana F. J., weiner H. L. Cutting Edge: Human Latency-associated Peptide+ T Cells: A Novel Regulatory T Cell Subset // J. Immunol. 2010. Vol. 184. P. 4620–4624.

20. Zhu Z. F., Meng K., Zhohg Y. C., Qi L., Mao X. B., Yu K. W., Zhang W., Zhu P. F., Ren Z. P., Wu B. W., Ji Q. W., Wang X., Zeng Q. T. Impaired circulating CD4+LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study // PLos ONE. 2014. Vol. 9 (2). e88775.

21. Lin Y.-Z., Lu Z.-H., Lu Z.-D., Huang Y., Shi Y., Liu L., Wang X.-Y., Ji Q.-W. Downregulation of CD4+LAP+ and CD4+CD25+ regulatory T cells in acute coronary syndromes // Med. Inflammation. 2013. Vol. 2013. P. 764082.

22. Valencia X., Stephens G., Goldbach-Mansky R., Wilson M., Stevach E. M., Lipsky P. E. TNF downmodulation the function of human CD4+CD25+hi T-regulatory cells // Blood. 2006. Vol. 108. P. 253–261.

23. Li Q., Wang Y., Chen K., Zhou Q., Wei W., Wang Y., Wang Y. The role of oxidized low-density lipoprotein in breaking peripheral Th17/Treg balance in patients with acute coronary syndrome // BBRC. 2010. Vol. 394. P. 836–842.

24. Feng J., Zhang Z., Kong W., Liu B., Xu Q., Wang X. Regulatory T cells ameliorate hyperhomocysteinaemiaaccelerated atherosclerosis in apoE-/- mice // Cardiovasc. Res. 2009. Vol. 84. P. 155–163.

25. Pasare C., Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells // Science. 2003. Vol. 299. P. 1033–1036.

26. Taleb S., Herbin O., Ait-Oufella H., Verreth W., Gourdy P., Barateau V., Merval R., Esposito B., Clement K., Holvoet P., Tedgui A., Mallat Z. Defective leptin/leptin receptor signaling improves regulatory T cell immune response and protects mice from atherosclerosis // Arterioscler. Thromb. Vasc. Biol. 2007. Vol. 27. P. 2691–2698.

27. Zhong Y., Wang X., Ji Q., Mao X., Tang H., Yi G., Meng K., Yang X., Zeng Q. CD4+LAP+ and CD4+CD25+Foxp3+ regulatory T cells induced by nasal oxidized low-density lipoprotein suppress effector T cell response and attenuate atherosclerosis in ApoE-/- mice // J. Clin. Immunol. 2012. Vol. 32. P. 1104–1117.

28. Sasaki N., Yamashita T., Takeda M., Shinohara M., Nakajiama K., Tawa H., Usui T., Hirata K.-I. Oral anti-CD3 antibody treatment induces regulatory T cells and inhibits the development of atherosclerosis in mice // Circulation. 2009. Vol. 120. P. 1996–2005.

29. Faria A. M., Weiner H. L. Oral tolerance // Immunol. Rev. 2005. Vol. 206. P. 232–259.

30. Dinh T. N., Kyaw T. S., Kanellakis P., To K., Tipping P., Toh B. H., Bobik A., Agrotis A. Cytokine therapy with interleukin-2/anti-interleukin-2 monoclonal antibody complexes expands CD4+CD25+Foxp3+regulatory T cells and attenuates development and progression of atherosclerosis // Circulation. 2012. Vol. 126. P. 1256–1266.

31. Klingenberg R., Lebens M., Hermansson A., Fredrikson G. N., Strodthoff D., Rudling M., Ketelhuth D. F. L., Gerdes N., Holmgren J., Nilsson J., Hansson G. K. Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis // Arterioscler. Thromb. Vasc. Biol. 2010. Vol. 30. P. 946–952.

32. Gotsman I., Gupta R., Lichtman A. H. The influence of the regulatory T lymphocytes on atherosclerosis // Arterioscler. Thromb. Vasc. Biol. 2007. Vol. 27. P. 2493–2495.

33. Van Brussel I., Schrijvers D. M., van Vre E. A., Bult H. Potential use of dendritic cells for anti-atherosclerotic therapy // Curr. Pharmaceutical Design. 2013. Vol. 19. P. 5873–5882.

34. Frodermann V., van Puijvelde G. H. M., Wierts L., Lagraauw H. M., Foks A. C., van Santbrink P. J., Bot I., Kuiper J., de Jager S. C. A. Oxidized low-density lipoprotein-induced apoptotic dendritic cells as a therapy for atherosclerosis // J. Immunol. 2015. Vol. 194. P. 1–11.

35. Javeed A., Zhang B., Qu Y., Zhang A., Sun C., Zhang L., Liu J., Zeng C., Zhao Y. The significantly enhanced frequency of functional CD4+CD25+Foxp3+T regulatory cells in therapeutic dose aspirin-treated mice // Transplant Immunol. 2009. Vol. 20. P. 253–260.

36. Takeda M., Yamashita T., Sasaki N., Nakajima K., Kita T., Shinohara M., Ishida T., Hirata K.-I. Oral administration of an active form of vitamin D3 (calcitriol) decreases atherosclerosis in mice by inducing regulatory T cells and immature dendritic cells with tolerogenic functions // Arterioscler. Thromb. Vasc. Biol. 2010. Vol. 30. P. 2495–2503.

37. Perry H. M., Bender T. P., McNamara C.A. B cell subsets in atherosclerosis // Front. Immunol. 2012. Vol. 3. P. 1–11.


Review

For citations:


Kozlov V.A. The suppressor cells – the basis of immunopathogenesis of atherosclerosis. Ateroscleroz. 2015;11(2):37-42. (In Russ.)

Views: 196


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2078-256X (Print)
ISSN 2949-3633 (Online)