Mesenchymal Stem Cell Modulates T Follicular Helper Cell to Induce Immunotolerance of Islet Allograft

Transplant Proc. 2015 Jul-Aug;47(6):2050-6. doi: 10.1016/j.transproceed.2015.05.030.

Abstract

Objective: To verify whether mesenchymal stem cells protected the islet allograft via modulating follicular B helper T cells (Tfh) cells.

Methods: The recipient mice were divided into 5 groups. Group A: the diabetic group (n = 12); Group B: islets alone group (n = 12); Group C: MSCs and islets co-transplanted group (n = 12, MSCs = 0.5 × 10(6)); Group D: MSCs and islets co-transplanted group (n = 12, MSCs = 1 × 10(6)); Group E: MSCs and islets co-transplanted group (n = 12, MSCs = 2 × 10(6)); One control group of normal NOD mice was set as well. ELISA was used to examine the autoantibody level of GAD65 Ab, insulin autoantibodies, and insulin. The Tfh count was determined by fluorescence-activated cell sorting. The insulin expression of islet grafts, the infiltration of lymphocytes, and the Tfh cells were observed via hematoxylin and eosin staining and immunohistochemical staining.

Results: There was significant prolonged graft survival and more insulin expression of islet grafts observed in the co-transplant group. A lower level of the Tfh cells and autoantibody GAD65 Ab, insulin autoantibodies were also presented in the co-transplant group (P < .01). The infiltration of lymphocytes in the co-transplant group was notably less than in the islet-alone group (P < .01).

Conclusions: Mesenchymal stem cells were able to protect the islet allograft by regulating the follicular helper T cells.

MeSH terms

  • Allografts / metabolism
  • Animals
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / surgery*
  • Female
  • Flow Cytometry
  • Graft Survival / immunology*
  • Immune Tolerance*
  • Islets of Langerhans Transplantation*
  • Mesenchymal Stem Cells / immunology*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • T-Lymphocytes, Helper-Inducer / immunology*