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Fenotypizace a kvantifikace T regulačních lymfocytů u pacientů s mnohočetným myelomem pomocí průtokové cytometrie


Authors: Muthu Raja K. R. 1,2;  L. Kovářová 1,3;  J. Štossová 1;  R. Hájek 1,3,4
Authors‘ workplace: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic 1;  Department of Molecular and Cellular Biology, Faculty of Science, Masaryk University, Brno, Czech Republic 2;  Laboratory of Experimental Hematology and Cell Immunotherapy, Department of Clinical Hematology, University Hospital Brno, Czech Republic 3;  Department of Internal Medicine – Hematooncology, University Hospital Brno, Czech Republic 4
Published in: Klin Onkol 2011; 24(Supplementum 1): 30-33

Overview

Mnohočetný myelom (MM) je onemocnění plazmatických buněk (PC), které bývá často spojeno s poruchami imunity. Fenotypizace a stanovení počtu regulačních T lymfocytů (Tregs) pomocí průtokové cytometrie může být využito k monitorování stavu imunity u myelomových pacientů. Charakterizace funkčního stavu Tregs pomocí proliferačních či inhibičních testů pak může odhalit jejich možnou poruchu. V naší studii bylo zjištěno, že u pacientů s MM jsou počty Tregs zvýšeny oproti zdravým kontrolám, což u těchto pacientů svědčí o deregulaci imunity.

Klíčová slova:
Treg buňky – flow cytometrie – mnohočetný myelom – thalidomid

Tato práce byla podpořena granty MŠMT ČR (MSM0021622434, LC06027), MZd ČR (IGA grants NS10406, NS10408) a GAČR GAP304/10/1395.

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Sources

1. Kyle RA, Rajkumar SV. Criteria for diagnosis staging risk stratification and response assessment of multiple myeloma. Leukemia 2009; 23(1): 3–9.

2. Raja KR, Kovarova L, Hajek R. Review of phenotypic markers used in flow cytometric analysis of MGUS and MM and applicability of flow cytometry in other plasma cell disorders. Br J Haematol 2010; 149(3): 334–351.

3. Mills KH, Cawley JC. Abnormal monoclonal antibody defined helper/suppressor T-cell subpopulations in multiple myeloma: relationship to treatment and clinical stage. Br J Haematol 1983; 53(2): 271–275.

4. Wolf AM, Wolf D, Steurer M et al. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003; 9(2): 606–612.

5. Fehérvari Z, Sakaguchi S. CD4+ Tregs and immune control. J Clin Invest 2004; 114(9): 1209–1217.

6. Bates GJ, Fox SB, Han C et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 2006; 24(34): 5373–5380.

7. Beyer M, Kochanek M, Darabi K et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood 2005; 106(6): 2018–2025.

8. Gambineri E, Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 2003; 15(4): 430–435.

9. Vieira PL, Christensen JR, Minaee S et al. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J Immunol 2004; 172(10): 5986–5993.

10. Chen W, Jin W, Hardegen N et al. Conversion of peripheral CD4+CD25-naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198(12): 1875–1886.

11. Fischer K, Voelkl S, Heymann J et al. Isolation and characterization of human antigen-specific TCR alpha beta+ CD4-CD8- double-negative regulatory T cells. Blood 2005; 105(7): 2828–2835.

12. Peng G, Wang HY, Peng W et al. Tumor-infiltrating gamma delta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity 2007; 27(2): 334–348.

13. Wang RF. CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Hum Immunol 2008; 69(11): 811–814.

14. Gil-Guerrero L, Dotor J, Huibregtse IL et al. In vitro and in vivo down-regulation of regulatory T cell activity with a peptide inhibitor of TGF-beta 1. J Immunol 2008; 181(1): 126–135.

15. Lieberman J. The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal. Nat Rev Immunol 2003; 3(5): 361–370.

16. Cao X. Regulatory T cells and immune tolerance to tumors. Immunol Res 2010; 46(1–3): 79–93.

17. Oderup C, Cederbom L, Makowska A et al. Cytotoxic T lymphocyte antigen-4 dependent down-modulation of costimulatory molecules on dendritic cells in CD4+CD25+ regulatory T-cell-mediated suppression. Immunology 2006; 118(2): 240–249.

18. Beyer M, Kochanek M, Giese T et al. In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma. Blood 2006; 107(10): 3940–3949.

19. Feyler S, von Lilienfeld-Toal M, Jarmin S et al. CD4+CD25+FoxP3+ regulatory T cells are increased whilst CD3+CD4-CD8-αβ TCR+ Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden. Br J Haematol 2009; 144(5): 686–695.

20. Prabhala RH, Neri P, Bae JE et al. Dysfunctional T regulatory cells in multiple myeloma. Blood 2006; 107(1): 301–304.

21. Gupta R, Ganeshan P, Hakim M et al. Significantly reduced regulatory T cell population in patients with untreated multiple myeloma. Leuk Res 2010. Epub of print.

22. Brimnes MK, Vangsted AJ, Knudsen LM et al. Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR–/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma. Scand J Immunol 2010; 72(6): 540–547.

23. Atanackovic D, Cao Y, Luetkens T et al. CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation. Haematologica 2008; 93(3): 423–430.

24. Wang X, Zheng J, Liu J et al. Increased population of CD4 (+) CD25 (high) regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients. Eur J Haematol 2005; 75(6): 468–476.

25. Yang ZZ, Novak AJ, Stenson MJ et al. Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T-cells in B-cell non-Hodgkin lymphoma. Blood 2006; 107(9): 3639–3646.

26. Giannopoulos K, Schmitt M, Własiuk P et al. The high frequency of T regulatory cells in patients with B-cell chronic lymphocytic leukemia is diminished through treatment with thalidomide. Leukemia 2008; 22(1): 222–224.

27. Quach H, Ritchie D, Stewart AK et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 2010; 24(1): 22–32.

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