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Treg cells in pancreatic lymph nodes： the possible role in diabetogenesis and βcell regeneration in a TID model

Cellular & Molecular Immunology 2012年第6期9卷 455-463页

作者： Benjamin K Nti Janet L Markman Suzanne Bertera Alexis J Styche Robert J Lakomy Vladimir M Subbotin Massimo Trucco Tatiana D Zorina Indiana University School of Medicine Indianapolis IN USA Cedars-Sinai Medical Center Los Angeles CA USA division of irnmunogenetics Children's Hospital of Pittsburgh University of Pittsburgh School of Medicine Pittsburgh PA USA Independent investigator 602 Samuel Dr. Madison Wl USA Department of Bioscience Technologies Jefferson School of Health Professions Thomas Jefferson University Philadelphia PA USA

Previously, we established a model in which physiologically adequate function of the autologous β cells was recovered in non-obese diabetic （NOD） mice after the onset of hyperglycemia by rendering them hemopoietic chimera. These mice were termed antea-diabetic. In the current study, we addressed the role of T regulatory （Treg） cells in the mechanisms mediating the restoration of euglycemia in the antea-diabetic NOD model. The data generated in this study demonstrated that the numbers of Treg cells were decreased in unmanipulated NOD mice, with the most profound deficiency detected in the pancreatic lymph nodes （PLNs）. The impaired retention of the Treg cells in the PLNs correlated with the locally compromised profile of the chemokines involved in their trafficking, with the most prominent decrease observed in SDF-1. The amelioration of autoimmunity and restoration of euglycemia observed in the antea-diabetic mice was associated with restoration of the Treg cell population in the PLNs. These data indicate that the function of the SDF-1/CXCR4 axis and the retention of Treg cells in the PLNs have a potential role in diabetogenesis and in the amelioration of autoimmunity and β cell regeneration in the antea-diabetic model. We have demonstrated in the antea-diabetic mouse model that lifelong recovery of the β cells has a strong correlation with normalization of the Treg cell population in the PLNs. This finding offers new opportunities for testing the immunomodulatory regimens that promote accumulation of Treg cells in the PLNs as a therapeutic approach for type 1 diabetes （TID）.

关键词： β cell regeneration T regulatory cell trafficking type 1 diabetes

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