CD33+ HLA-DR– Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset


  • Mirhane Hassan Clinical and Chemical Pathology Department, National Research Center, Dokki
  • Hala M. Raslan Internal Medicine Department, National Research Center, Dokki
  • Hesham Gamal Eldin Clinical and Chemical Pathology Department, National Research Center, Dokki
  • Eman Mahmoud Clinical and Chemical Pathology Department, National Research Center, Dokki
  • Hanaa Alm-elhuda Abd Elwajed Clinical and Chemical Pathology Department, National Research Center, Dokki



Myeloid-derived suppressor cells, Type 1 Diabetes, Diabetic nephropathy, CD 14 , MDSCs subsets


INTRODUCTION: Type 1 Diabetes Mellitus (T1D) is an autoimmune disease that results from the destruction of insulin-producing beta cells of the pancreas by autoreactive T cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that can potently suppress T cell responses.

AIM: To detect the presence of MDSCs in T1D and compare their percentage in T1D versus healthy individuals.

METHOD: Thirty T1D patients were included in the study. Diabetic patients with nephropathy (n = 18) and diabetic patients without nephropathy (n = 12). A control group of healthy individuals (n = 30) were also included. CD33+ and HLA-DR– markers were used to identify MDSCs by flow cytometry. CD14 positive and negative MDSCs subsets were also identified.

RESULTS: MDSCs was significantly increased in T1D than the control group and diabetic patient with nephropathy compared to diabetic patients without nephropathy. M-MDSCs (CD14+ CD33+ HLA–DR−) were the most abundant MDSCs subpopulation in all groups, however their percentage decrease in T1D than the control group.

CONCLUSION: MDSCs are increased in the peripheral blood of T1D with a predominance of the CD14+ MDSCs subset. Future studies are needed to test the immune suppression function of MDSCs in T1D.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Ermann J, Fathman CG. Autoimmune diseases: genes, bugs and failed regulation. Nature Immunology. 2001; 2(9):759-761.

Yang WC. Myeloid-derived Suppressor Cells in Autoimmune Diabetes: Their Anti-diabetic Potential and Mechanism. J Diabetes Metab S. 2013; 12:2.

Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014; 383(9911):69–82.

Pasquali L, Giannoukakis N, Trucco M. Induction of immune tolerance to facilitate β cell regeneration in type 1 diabetes. Advanced drug delivery reviews. 2008; 60(2):106-13. PMid:18053613

Hu C, Du W, Zhang X, Wong FS, Wen L. The role of Gr1+ cells after anti-CD20 treatment in type 1 diabetes in nonobese diabetic mice. The Journal of Immunology. 2012; 188(1):294-301. PMid:22140261 PMCid:PMC4361178

Ribechini E, Greifenberg V, Sandwick S, Lutz MB. Subsets, expansion and activation of myeloid-derived suppressor cells. Medical microbiology and immunology. 2010; 199(3):273-81. PMid:20376485

Richardson SJ, Willcox A, Bone AJ, Morgan NG, Foulis AK. Immunopathology of the human pancreas in type-I diabetes. Seminars in immunopathology. 2011; 33(1):9-21. PMid:20424842

Filipazzi P, Huber V, Rivoltini L. Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunology, Immunotherapy. 2012; 61(2):255-63. PMid:22120756

Atretkhany KS, Drutskaya MS. Myeloid-derived suppressor cells and proinflammatory cytokines as targets for cancer therapy. Biochemistry (Moscow). 2016; 81(11):1274-83. PMid:27914453

Youn JI, Gabrilovich DI. The biology of myeloidâ€derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. European journal of immunology. 2010; 40(11):2969-75. PMid:21061430 PMCid:PMC3277452

Youn JI, Nagaraj S, Collazo M, Gabrilovich DI. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. The Journal of Immunology. 2008; 181(8):5791-802. PMid:18832739 PMCid:PMC2575748

Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, Mandruzzato S, Bronte V. Myeloid-derived suppressor cell heterogeneity and subset definition. Current opinion in immunology. 2010; 22(2):238-44. PMid:20171075

Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nature reviews immunology. 2009; 9(3):162. PMid:19197294 PMCid:PMC2828349

Talmadge JE, Gabrilovich DI. History of myeloid-derived suppressor cells. Nature Reviews Cancer. 2013; 13(10):739. PMid:24060865 PMCid:PMC4358792

Gielen PR, Schulte BM, Kers-Rebel ED, Verrijp K, Petersen-Baltussen HM, Ter Laan M, Wesseling P, Adema GJ. Increase in both CD14-positive and CD15-positive myeloid-derived suppressor cell subpopulations in the blood of patients with glioma but predominance of CD15-positive myeloid-derived suppressor cells in glioma tissue. Journal of neuropathology & experimental neurology. 2015; 74(5):390-400. PMid:25853692

Lindau D, Gielen P, Kroesen M, Wesseling P, Adema GJ. The immunosuppressive tumour network: myeloidâ€derived suppressor cells, regulatory T cells and natural killer T cells. Immunology. 2013; 138(2):105-15. PMid:23216602 PMCid:PMC3575763

Yin B, Ma G, Yen CY, Zhou Z, Wang GX, Divino CM, Casares S, Chen SH, Yang WC, Pan PY. Myeloid-derived suppressor cells prevent type 1 diabetes in murine models. The Journal of Immunology. 2010; 185(10):5828-34. PMid:20956337 PMCid:PMC4355963

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes care. 2010; 33(Suppl 1):S62. PMid:20042775 PMCid:PMC2797383

Nazar CM. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease. Journal of nephropharmacology. 2014; 3(1):15.

Luan Y, Mosheir E, Menon MC, Wilson D, Woytovich C, Ochando J, Murphy B. Monocytic Myeloidâ€Derived Suppressor Cells Accumulate in Renal Transplant Patients and Mediate CD4+ Foxp3+ Treg Expansion. American journal of transplantation. 2013; 13(12):3123-31. PMid:24103111

Zhang Q, Fujino M, Xu J, Li XK. The role and potential therapeutic application of myeloid-derived suppressor cells in allo-and autoimmunity. Mediators of inflammation. 2015; Article ID 421927:1-14.

Whitfield-Larry F, Felton J, Buse J, Su MA. Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients. Clinical Immunology. 2014; 153(1):156-64. PMid:24769355

Kracht MJ, Zaldumbide A, Roep BO. Neoantigens and microenvironment in type 1 diabetes: lessons from antitumor immunity. Trends in Endocrinology & Metabolism. 2016; 27(6):353-62. PMid:27094501

Piemonti L, Leone BE, Nano R, Saccani A, Monti P, Maffi P, Bianchi G, Sica A, Peri G, Melzi R, Aldrighetti L. Human pancreatic islets produce and secrete MCP-1/CCL2: relevance in human islet transplantation. Diabetes. 2002; 51(1):55-65. PMid:11756323

Roep BO, Kleijwegt FS, Van Halteren AG, Bonato V, Boggi U, Vendrame F, Marchetti P, Dotta F. Islet inflammation and CXCL10 in recentâ€onset type 1 diabetes. Clinical & Experimental Immunology. 2010; 159(3):338-43. PMid:20059481 PMCid:PMC2819499

Büll C, den Brok MH, Adema GJ. Sweet escape: sialic acids in tumor immune evasion. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2014; 1846(1):238-46. PMid:25026312

Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nature medicine. 2013; 19(11):1423. PMid:24202395 PMCid:PMC3954707

Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, Roep BO, von Herrath MG. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. Journal of Experimental Medicine. 2012: jem-20111187.

Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and β-cell loss in type 1 diabetes. Nature Reviews Endocrinology. 2009; 5(4):219. PMid:19352320

Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140(6):883-99. PMid:20303878 PMCid:PMC2866629

Motallebnezhad M, Jadidi-Niaragh F, Qamsari E S, et al. The immunobiology of myeloid-derived suppressor cells in cancer. Tumor Biology. 2015; 37(2):1387-1406. PMid:26611648

Haile LA, Von Wasielewski R, Gamrekelashvili J, Krüger C, Bachmann O, Westendorf AM, Buer J, Liblau R, Manns MP, Korangy F, Greten TF. Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology. 2008; 135(3):871-81. PMid:18674538

Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nature reviews immunology. 2009; 9(3):162. PMid:19197294 PMCid:PMC2828349

Lechner MG, Liebertz DJ, Epstein AL. Correction: Characterization of Cytokine-Induced Myeloid-Derived Suppressor Cells from Normal Human Peripheral Blood Mononuclear Cells. The Journal of Immunology. 2010; 185(9):5668-5668.

Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, Kaiser N, Halban PA, Donath MY. Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. The Journal of clinical investigation. 2002; 110(6):851-60. PMid:12235117 PMCid:PMC151125

Campbell IL, Kay TW, Oxbrow L, Harrison LC. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice. The Journal of clinical investigation. 1991; 87(2):739-42. PMid:1899431 PMCid:PMC296368

Xing YF, Cai RM, Lin Q, Ye QJ, Ren JH, Yin LH, Li X. Expansion of polymorphonuclear myeloid-derived suppressor cells in patients with end-stage renal disease may lead to infectious complications. Kidney international. 2017; 91(5):1236-42. PMid:28215666

Greten TF, Manns MP, Korangy F. Myeloid derived suppressor cells in human diseases. International immunopharmacology. 2011; 11(7):802-7. PMid:21237299 PMCid:PMC3478130

Ning G, She L, Lu L, Liu Y, Zeng Y, Yan Y, Lin C. Analysis of monocytic and granulocytic myeloid-derived suppressor cells subsets in patients with hepatitis C virus infection and their clinical significance. BioMed research international. 2015; 2015:1-8.



How to Cite

Hassan M, Raslan HM, Eldin HG, Mahmoud E, Abd Elwajed HA- elhuda. CD33+ HLA-DR– Myeloid-Derived Suppressor Cells Are Increased in Frequency in the Peripheral Blood of Type1 Diabetes Patients with Predominance of CD14+ Subset. Open Access Maced J Med Sci [Internet]. 2018 Feb. 9 [cited 2022 Aug. 14];6(2):303-9. Available from:



B - Clinical Sciences

Most read articles by the same author(s)