Exp Clin Endocrinol Diabetes 2014; 122(1): 27-30
DOI: 10.1055/s-0033-1358666
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Percentage of Circulating CD8+ T Lymphocytes is Associated with Albuminuria in Type 2 Diabetes Mellitus

L. Lei
1   Division of Hematology and Endocrinology, Peking University Aerospace Center Hospital, Beijing, China
,
Y. Mao
2   Department of Cardiology, Peking University First Hospital, Beijing, China
3   Department of Biochemistry, National Cerebral and Cardiovascular Center, Osaka, Japan
,
D. Meng
1   Division of Hematology and Endocrinology, Peking University Aerospace Center Hospital, Beijing, China
,
X. Zhang
1   Division of Hematology and Endocrinology, Peking University Aerospace Center Hospital, Beijing, China
,
L. Cui
1   Division of Hematology and Endocrinology, Peking University Aerospace Center Hospital, Beijing, China
,
Y. Huo
2   Department of Cardiology, Peking University First Hospital, Beijing, China
,
Y. Wang
1   Division of Hematology and Endocrinology, Peking University Aerospace Center Hospital, Beijing, China
› Author Affiliations
Further Information

Publication History

received 11 July 2013
first decision 22 September 2013

accepted 09 October 2013

Publication Date:
07 November 2013 (online)

Abstract

T lymphocytes have been demonstrated to play a role in the development of diabetic proteinuria. However, the alteration of circulating T lymphocytes has not been investigated in a type 2 diabetic cohort. A cross-sectional study was conducted in Peking University Aerospace Center Hospital. 510 participants were type 2 diabetes mellitus, 30–70 years of age. Patients with immune disease, medical conditions that affect immune function, infection, or end-organ damage were excluded. The percentage of circulating CD8+ T lymphocytes was significantly associated with albuminuria in the cohort. The impact of albuminuria to CD8+ T lymphocytes in a multivariate linear regression model was indicated by the B- coefficient (95% confidence interval) 1.812 (0.204–3.421, P=0.03). Our data first showed that the percentage of circulating CD8+ T cells is associated with albuminuria in type 2 diabetes mellitus, which may support the rationality of systemic inhibition of T lymphocytes in treating albuminuria in these patients.

 
  • References

  • 1 Remuzzi G, Schieppati A, Ruggenenti P. Nephropathy in patients with type 2 diabetes. N Engl J Med 2002; 346: 1145-1151
  • 2 Caramori ML, Mauer M. Diabetes and nephropathy. Curr Opin Nephrol Hypertens 2003; 12: 273-282
  • 3 Wolf G, Ritz E. Diabetic nephropathy in type 2 diabetes prevention and patient management. J Am Soc Nephrol 2003; 14: 1396-1405
  • 4 Dronavalli S, Duka I, Bakris GL. The pathogenesis of diabetic nephropathy. Nat Clin Pract Endocrinol Metab 2008; 4: 444-452
  • 5 Adler AI, Stevens RJ, Manley SE et al. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 2003; 63: 225-232
  • 6 Xiao X, Ma B, Dong B et al. Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice. J Autoimmun 2009; 32: 85-93
  • 7 Moon JY, Jeong KH, Lee TW et al. Aberrant recruitment and activation of T cells in diabetic nephropathy. Am J Nephrol 2012; 35: 164-174
  • 8 Moriya R, Manivel JC, Mauer M. Juxtaglomerular apparatus T-cell infiltration affects glomerular structure in Type 1 diabetic patients. Diabetologia 2004; 47: 82-88
  • 9 Bending JJ, Lobo-Yeo A, Vergani D et al. Proteinuria and activated T-lymphocytes in diabetic nephropathy. Diabetes 1988; 37: 507-511
  • 10 Lim AK, Ma FY, Nikolic-Paterson DJ et al. Lymphocytes promote albuminuria, but not renal dysfunction or histological damage in a mouse model of diabetic renal injury. Diabetologia 2010; 53: 1772-1782
  • 11 Giordano C, De Maria R, Todaro M et al. Study of T-cell activation in type 1 diabetic patients and pre-type I diabetic subjects by cytometric analysis: antigen expression defect in vitro. J Clin Immunol 1993; 13: 68-78
  • 12 Gessl A, Waldhäusl W. Increased CD69 and human leukocyte antigen-DR expression on T lymphocytes in insulin-dependent diabetes mellitus of long standing. J Clin Endocrinol Metab 1998; 83: 2204-2209
  • 13 Ha H, Yu MR, Choi YJ et al. Role of high glucose-induced nuclear factor-κB activation in monocyte chemoattractant protein-1 expression by mesangial cells. J Am Soc Nephrol 2002; 13: 894-902
  • 14 Chen JS, Lee HS, Jin JS et al. Attenuation of mouse mesangial cell contractility by high glucose and mannitol: involvement of protein kinase C and focal adhesion kinase. J Biomed Sci 2004; 11: 142-151
  • 15 Imani F, Horii Y, Suthanthiran M et al. Advanced glycosylation endproduct-specific receptors on human and rat T lymphocytes mediate synthesis of interferon γ: role in tissue remodeling. J Exp Med 1993; 178: 2165-2172
  • 16 Wen Y, Gu J, Li SL et al. Elevated glucose and diabetes promote interleukin-12 cytokine gene expression in mouse macrophages. Endocrinology 2006; 147: 2518-2525
  • 17 Bohlender JM, Franke S, Stein G et al. Advanced glycation end products and the kidney. Am J Physiol Renal Physiol 2005; 289: F645-F659
  • 18 Goh SY, Cooper ME. The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93: 1143-1152
  • 19 Mezzano S, Droguett A, Burgos ME et al. Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney Int suppl 2003; 86: S64-S70
  • 20 Lee FT, Cao Z, Long DM et al. Interactions between angiotensin II and NF-κB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy. J Am Soc Nephrol 2004; 15: 2139-2151
  • 21 Kanetsuna Y, Takahashi K, Nagata M et al. Deficiency of endothelial nitric-oxide synthase confers susceptibility to diabetic nephropathy in nephropathy-resistant inbred mice. Am J of Pathol 2007; 170: 1473-1484
  • 22 Eller K, Kirsch A, Wolf AM et al. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes 2011; 60: 2954-2962
  • 23 Zeng C, Shi X, Zhang B et al. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. Journal of molecular medicine 2012; 90: 175-186
  • 24 Utimura R, Fujihara CK, Mattar AL et al. Mycophenolate mofetil prevents the development of glomerular injury in experimental diabetes. Kidney Int 2003; 63: 209-216
  • 25 Meyer TW. Immunosuppression for diabetic glomerular disease?. Kidney Int 2003; 63: 377-378
  • 26 Han SY, Kim CH, Kim HS et al. Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. J Am Soc Nephrol 2006; 17: 1362-1372
  • 27 Rivero A, Mora C, Muros M et al. Pathogenic perspectives for the role of inflammation in diabetic nephropathy. Clin Sci 2009; 116: 479-492
  • 28 Turgut F, Bolton WK. Potential new therapeutic agents for diabetic kidney disease. Am J Kidney Dis 2010; 55: 928-940
  • 29 Sakaguchi M, Isono M, Isshiki K et al. Inhibition of mTOR signaling with rapamycin attenuates renal hypertrophy in the early diabetic mice. Biochem Biophys Res Commun 2006; 340: 296-301
  • 30 Lloberas N, Cruzado JM, Franquesa M et al. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 2006; 17: 1395-1404
  • 31 Yang Y, Wang J, Qin L et al. Rapamycin prevents early steps of the development of diabetic nephropathy in rats. Am J of Nephrol 2007; 27: 495-502
  • 32 Mori H, Inoki K, Masutani K et al. The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential. Biochem Biophys Res Commun 2009; 384: 471-475