Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients

被引:58
作者
Whitfield-Larry, Fatima [1 ,2 ]
Felton, Jamie [1 ]
Buse, John [3 ]
Su, Maureen A. [1 ,2 ]
机构
[1] Univ N Carolina, Sch Med, Dept Pediat, Div Endocrinol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Sch Med, Dept Med, Div Endocrinol, Chapel Hill, NC 27599 USA
关键词
Myeloid-derived suppressor cells; T cell suppression; Type 1 diabetes mellitus; PANCREATIC-ISLETS; NOD MICE; CANCER; ACTIVATION; DISTINCT; PATHWAY; CLONES;
D O I
10.1016/j.clim.2014.04.006
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Type 1 Diabetes Mellitus (T1D) results from the destruction of insulin-producing beta cells in the pancreas by autoreactive T cells. Myeloid derived suppressor cells (MDSCs) are a recently identified immune cell subset that down-regulate T cells. Whether defects in MDSC numbers or function may contribute to T1D pathogenesis is not known. We report here that MDSCs are unexpectedly enriched in peripheral blood of both mice and patients with autoimmune diabetes. Peripheral blood MDSCs from T1D patients suppressed T cell proliferation in a contact-dependent manner; however, suppressive function could be enhanced with in vitro cytokine induction. These findings suggest that native T1D MDSCs are not maximally suppressive and that strategies to promote MDSC suppressive function may be effective in preventing or treating T1D. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:156 / 164
页数:9
相关论文
共 30 条
[1]
Bingisser RM, 1998, J IMMUNOL, V160, P5729
[2]
Genetics, pathogenesis and clinical interventions in type 1 diabetes [J].
Bluestone, Jeffrey A. ;
Herold, Kevan ;
Eisenbarth, George .
NATURE, 2010, 464 (7293) :1293-1300
[3]
ESSENTIAL ROLE FOR INTERFERON-GAMMA AND INTERLEUKIN-6 IN AUTOIMMUNE INSULIN-DEPENDENT DIABETES IN NOD/WEHI MICE [J].
CAMPBELL, IL ;
KAY, TWH ;
OXBROW, L ;
HARRISON, LC .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (02) :739-742
[4]
Mechanism Regulating Reactive Oxygen Species in Tumor-Induced Myeloid-Derived Suppressor Cells [J].
Corzo, Cesar A. ;
Cotter, Matthew J. ;
Cheng, Pingyan ;
Cheng, Fendong ;
Kusmartsev, Sergei ;
Sotomayor, Eduardo ;
Padhya, Tapan ;
McCaffrey, Thomas V. ;
McCaffrey, Judith C. ;
Gabrilovich, Dmitry I. .
JOURNAL OF IMMUNOLOGY, 2009, 182 (09) :5693-5701
[5]
MDSC in autoimmunity [J].
Cripps, James G. ;
Gorham, James D. .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2011, 11 (07) :789-793
[6]
FLEMING TJ, 1993, J IMMUNOL, V151, P2399
[7]
Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging [J].
Fu, Wenxian ;
Wojtkiewicz, Gregory ;
Weissleder, Ralph ;
Benoist, Christophe ;
Mathis, Diane .
NATURE IMMUNOLOGY, 2012, 13 (04) :361-368
[8]
The terminology issue for myeloid-derived suppressor cells [J].
Gabrilovich, Dmitry I. ;
Bronte, Vincenzo ;
Chen, Shu-Hsia ;
Colombo, Mario P. ;
Ochoa, Augusto ;
Ostrand-Rosenberg, Suzanne ;
Schreiber, Hans .
CANCER RESEARCH, 2007, 67 (01) :425-425
[9]
Myeloid-derived suppressor cells as regulators of the immune system [J].
Gabrilovich, Dmitry I. ;
Nagaraj, Srinivas .
NATURE REVIEWS IMMUNOLOGY, 2009, 9 (03) :162-174
[10]
PATHOLOGIC ANATOMY OF PANCREAS IN JUVENILE DIABETES MELLITUS [J].
GEPTS, W .
DIABETES, 1965, 14 (10) :619-+