Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation

PLoS One. 2015 May 28;10(5):e0128494. doi: 10.1371/journal.pone.0128494. eCollection 2015.

Abstract

Type I diabetes (T1D), mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC) transplantation. Older non-obese diabetic (NOD) mice recipients (3m, at disease-onset stage) receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage). FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg) and lower proportion of proliferating T conventional cells (Tcon) in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN), blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Aging / pathology
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Biomarkers / metabolism
  • Blood Glucose / immunology
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / mortality
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy
  • Disease Models, Animal
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Gene Expression
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Immunophenotyping
  • Lymphocyte Count
  • Mice
  • Mice, Inbred NOD
  • Survival Analysis
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Whole-Body Irradiation

Substances

  • Antigens, CD
  • Biomarkers
  • Blood Glucose
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse