Functional Status of Immune Cells in Patients with Long-lasting Type 2 Diabetes Mellitus

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2018 Jul 20

PMID 30022471

Citations 8

Authors

H W Nam

Y J Cho

J A Lim

S J Kim

H Kim

S Y Sim

D G Lim

Affiliations

Soon will be listed here.

Abstract

Although patients with diabetes contract infectious diseases at higher frequencies, and in more severe forms, compared to non-diabetics, the underlying defects of the immune function have not been defined clearly. To address this, we designed an immune monitoring protocol and analysed the functional status of various immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with the proper ligands and the functional reactivity of each lineage of cells was subsequently measured. Patients with type 2 diabetes mellitus (T2DM) had PBMC composition ratios comparable to healthy controls, except for a higher frequency of B cell and effector T cell fractions. The capacity of myeloid cells to secrete proinflammatory cytokines was not diminished in terms of the sensitivity and magnitude of the response. Furthermore, cytolytic activity and interferon (IFN)-γ production of natural killer (NK) cells and CD8 T cells were not decreased in T2DM patients. Phenotypical maturation of dendritic cells, indicated by the up-regulation of major histocompatibility complex (MHC) proteins and co-stimulatory molecules in response to lipopolysaccharide (LPS), was slightly enhanced in T2DM patients. Finally, the functional differentiation profiles of CD4 T cells did not differ between T2DM patients and the control group. These data indicate that patients with long-lasting T2DM do not have any gross functional defects in immune cells, at least in circulating monocytes, dendritic cells, NK cells and T lymphocytes.

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References

Kumar N, Sridhar R, Nair D, Banurekha V, Nutman T, Babu S . Type 2 diabetes mellitus is associated with altered CD8(+) T and natural killer cell function in pulmonary tuberculosis. Immunology. 2014; 144(4):677-86. PMC: 4368174. DOI: 10.1111/imm.12421. View

Smyth M, Godfrey D, Trapani J . A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol. 2001; 2(4):293-9. DOI: 10.1038/86297. View

Reizis B, Bunin A, Ghosh H, Lewis K, Sisirak V . Plasmacytoid dendritic cells: recent progress and open questions. Annu Rev Immunol. 2011; 29:163-83. PMC: 4160806. DOI: 10.1146/annurev-immunol-031210-101345. View

Brodin P, Jojic V, Gao T, Bhattacharya S, Lopez Angel C, Furman D . Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015; 160(1-2):37-47. PMC: 4302727. DOI: 10.1016/j.cell.2014.12.020. View

Graber R, Farine J, Fumagalli I, Tatti V, Losa G . Apoptosis and oxidative status in peripheral blood mononuclear cells of diabetic patients. Apoptosis. 2003; 4(4):263-70. DOI: 10.1023/a:1026408409916. View

Komura T, Sakai Y, Honda M, Takamura T, Matsushima K, Kaneko S . CD14+ monocytes are vulnerable and functionally impaired under endoplasmic reticulum stress in patients with type 2 diabetes. Diabetes. 2009; 59(3):634-43. PMC: 2828670. DOI: 10.2337/db09-0659. View

Joshi N, Caputo G, Weitekamp M, Karchmer A . Infections in patients with diabetes mellitus. N Engl J Med. 1999; 341(25):1906-12. DOI: 10.1056/NEJM199912163412507. View

Zhu J, Paul W . Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol Rev. 2010; 238(1):247-62. PMC: 2975272. DOI: 10.1111/j.1600-065X.2010.00951.x. View

Piatkiewicz P, Milek T, Bernat-Karpinska M, Ohams M, Czech A, Ciostek P . The dysfunction of NK cells in patients with type 2 diabetes and colon cancer. Arch Immunol Ther Exp (Warsz). 2013; 61(3):245-53. DOI: 10.1007/s00005-013-0222-5. View

10.

Touch S, Clement K, Andre S . T Cell Populations and Functions Are Altered in Human Obesity and Type 2 Diabetes. Curr Diab Rep. 2017; 17(9):81. DOI: 10.1007/s11892-017-0900-5. View

11.

Hatanaka E, Monteagudo P, Marrocos M, Campa A . Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes. Clin Exp Immunol. 2006; 146(3):443-7. PMC: 1810405. DOI: 10.1111/j.1365-2249.2006.03229.x. View

12.

Kalokhe A, Adekambi T, Ibegbu C, Ray S, Day C, Rengarajan J . Impaired degranulation and proliferative capacity of Mycobacterium tuberculosis-specific CD8+ T cells in HIV-infected individuals with latent tuberculosis. J Infect Dis. 2014; 211(4):635-40. PMC: 4351361. DOI: 10.1093/infdis/jiu505. View

13.

Vargas-Rojas M, Ramirez-Venegas A, Limon-Camacho L, Ochoa L, Hernandez-Zenteno R, Sansores R . Increase of Th17 cells in peripheral blood of patients with chronic obstructive pulmonary disease. Respir Med. 2011; 105(11):1648-54. DOI: 10.1016/j.rmed.2011.05.017. View

14.

Berrou J, Fougeray S, Venot M, Chardiny V, Gautier J, Dulphy N . Natural killer cell function, an important target for infection and tumor protection, is impaired in type 2 diabetes. PLoS One. 2013; 8(4):e62418. PMC: 3636194. DOI: 10.1371/journal.pone.0062418. View

15.

Giulietti A, van Etten E, Overbergh L, Stoffels K, Bouillon R, Mathieu C . Monocytes from type 2 diabetic patients have a pro-inflammatory profile. 1,25-Dihydroxyvitamin D(3) works as anti-inflammatory. Diabetes Res Clin Pract. 2006; 77(1):47-57. DOI: 10.1016/j.diabres.2006.10.007. View

16.

Li Y, Oosting M, Smeekens S, Jaeger M, Aguirre-Gamboa R, Le K . A Functional Genomics Approach to Understand Variation in Cytokine Production in Humans. Cell. 2016; 167(4):1099-1110.e14. DOI: 10.1016/j.cell.2016.10.017. View

17.

Dolff S, Bijl M, Huitema M, Limburg P, Kallenberg C, Abdulahad W . Disturbed Th1, Th2, Th17 and T(reg) balance in patients with systemic lupus erythematosus. Clin Immunol. 2011; 141(2):197-204. DOI: 10.1016/j.clim.2011.08.005. View

18.

Maecker H, McCoy J, Nussenblatt R . Standardizing immunophenotyping for the Human Immunology Project. Nat Rev Immunol. 2012; 12(3):191-200. PMC: 3409649. DOI: 10.1038/nri3158. View

19.

Delamaire M, Maugendre D, Moreno M, Le Goff M, Allannic H, GENETET B . Impaired leucocyte functions in diabetic patients. Diabet Med. 1997; 14(1):29-34. DOI: 10.1002/(SICI)1096-9136(199701)14:1<29::AID-DIA300>3.0.CO;2-V. View

20.

Jagannathan-Bogdan M, McDonnell M, Shin H, Rehman Q, Hasturk H, Apovian C . Elevated proinflammatory cytokine production by a skewed T cell compartment requires monocytes and promotes inflammation in type 2 diabetes. J Immunol. 2010; 186(2):1162-72. PMC: 3089774. DOI: 10.4049/jimmunol.1002615. View