Maternal microchimerism: increased in the insulin positive compartment of type 1 diabetes pancreas but not in infiltrating immune cells or replicating islet cells.
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.


CONCLUSIONS
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.
Diabetes and Metabolism Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
Jody
J
Ye
Immunology Department, Institut de Recerca Germans Trias i Pujol, Carretera Canyet s/n, Badalona, Spain.
Marta
M
Vives-Pi
Diabetes and Metabolism Unit, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom.
Kathleen M
KM
Gillespie
D000293:Adolescent; D000328:Adult; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D041321:Chromosomes, Human, X / Q000235:genetics / Q000276:immunology; D041322:Chromosomes, Human, Y / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D050991:GATA4 Transcription Factor / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D007328:Insulin / Q000276:immunology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics / Q000276:immunology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000196:embryology / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D055815:Young Adult
D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D007328:Insulin; D019394:Ki-67 Antigen