Maternal Microchimerism: Increased in the Insulin Positive Compartment of Type 1 Diabetes Pancreas but Not in Infiltrating Immune Cells or Replicating Islet Cells

被引:19
作者
Ye, Jody [1 ]
Vives-Pi, Marta [2 ]
Gillespie, Kathleen M. [1 ]
机构
[1] Univ Bristol, Sch Clin Sci, Diabet & Metab Unit, Bristol, Avon, England
[2] Inst Recerca Germans Trias & Pujol, Dept Immunol, Badalona, Spain
关键词
BETA-CELLS; T-CELLS; ENDOCRINE; EXPANSION; ANTIGENS;
D O I
10.1371/journal.pone.0086985
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: Maternal microchimeric cells (MMc) transfer across the placenta during pregnancy. Increased levels of MMc have been observed in several autoimmune diseases including type 1 diabetes but their role is unknown. It has been suggested that MMc are 1) effector cells of the immune response, 2) targets of the autoimmune response or 3) play a role in tissue repair. The aim of this study was to define the cellular phenotype of MMc in control (n = 14) and type 1 diabetes pancreas (n = 8). Methods: Using sex chromosome-based fluorescence in-situ hybridization, MMc were identified in male pancreas and their phenotype determined by concomitant immunofluorescence. Results: In normal pancreas, MMc positive for endocrine, exocrine, duct and acinar markers were identified suggesting that these cells are derived from maternal progenitors. Increased frequencies of MMc were observed in type 1 diabetes pancreas (p = 0.03) with particular enrichment in the insulin positive fraction (p = 0.01). MMc did not contribute to infiltrating immune cells or Ki67+ islet cell populations in type 1 diabetes. Conclusion: These studies provide support for the hypothesis that MMc in human pancreas are derived from pancreatic precursors. Increased frequencies of MMc beta cells may contribute to the initiation of autoimmunity or to tissue repair but do not infiltrate islets in type 1 diabetes.
引用
收藏
页数:7
相关论文
共 24 条
[1]   Transdifferentiation of pancreatic ductal cells to endocrine β-cells [J].
Bonner-Weir, Susan ;
Inada, Akari ;
Yatoh, Shigeru ;
Li, Wan-Chun ;
Aye, Tandy ;
Toschi, Elena ;
Sharma, Arun .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2008, 36 :353-356
[2]   The effect of tolerance to noninherited maternal HLA antigens on the survival of renal transplants from sibling donors [J].
Burlingham, WJ ;
Grailer, AP ;
Heisey, DM ;
Claas, FHJ ;
Norman, D ;
Mohanakumar, T ;
Brennan, DC ;
De Fijter, H ;
Van Gelder, T ;
Pirsch, JD ;
Sollinger, HW ;
Bean, MA .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (23) :1657-1664
[3]  
Dutta Partha, 2010, Chimerism, V1, P2, DOI 10.4161/chim.1.1.12667
[4]   DIPLOID, TETRAPLOID AND OCTAPLOID BETA CELLS IN ISLETS OF LANGERHANS OF NORMAL HUMAN PANCREAS [J].
EHRIE, MG ;
SWARTZ, FJ .
DIABETES, 1974, 23 (07) :583-588
[5]   Generation and expansion of multipotent mesenchymal progenitor cells from cultured human pancreatic islets [J].
Gallo, R. ;
Gambelli, F. ;
Gava, B. ;
Sasdelli, F. ;
Tellone, V. ;
Masini, M. ;
Marchetti, P. ;
Dotta, F. ;
Sorrentino, V. .
CELL DEATH AND DIFFERENTIATION, 2007, 14 (11) :1860-1871
[6]  
Karafin MS, 2010, INT J CLIN EXP PATHO, V3, P47
[7]   Transcription factor GATA-6 is expressed in the endocrine and GATA-4 in the exocrine pancreas [J].
Ketola, I ;
Otonkoski, T ;
Pulkkinen, MA ;
Niemi, H ;
Palgi, J ;
Jacobsen, CM ;
Wilson, DB ;
Heikinheimo, M .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2004, 226 (1-2) :51-57
[8]   β-Cell replication is the primary mechanism subserving the postnatal expansion of β-cell mass in humans [J].
Meier, Juris J. ;
Butler, Alexandra E. ;
Saisho, Yoshifumi ;
Monchamp, Travis ;
Galasso, Ryan ;
Bhushan, Anil ;
Rizza, Robert A. ;
Butler, Peter C. .
DIABETES, 2008, 57 (06) :1584-1594
[9]   Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in Utero [J].
Mold, Jeff E. ;
Michaelsson, Jakob ;
Burt, Trevor D. ;
Muench, Marcus O. ;
Beckerman, Karen P. ;
Busch, Michael P. ;
Lee, Tzong-Hae ;
Nixon, Douglas F. ;
McCune, Joseph M. .
SCIENCE, 2008, 322 (5907) :1562-1565
[10]  
Neelson JL, 2008, SCI AM, V298, P72