Diabetes in non-obese diabetic mice is not associated with quantitative changes in CD4+ CD25+ Foxp3+ regulatory T cells

Richard J Mellanby, David Thomas, Jenny M Phillips, Anne Cooke

Research output: Contribution to journalArticlepeer-review

Abstract

The role of regulatory T cells (Tregs) in maintaining self tolerance has been intensively researched and there is a growing consensus that a decline in Treg function is an important step towards the development of autoimmune diseases, including diabetes. Although we show here that CD25+ cells delay diabetes onset in non-obese diabetic (NOD) mice, we found, in contrast to previous reports, neither an age-related decline nor a decline following onset of diabetes in the frequency of CD4+ CD25+ Foxp3+ regulatory T cells. Furthermore, we demonstrate that CD4+ CD25+ cells from both the spleen and pancreatic draining lymph nodes of diabetic and non-diabetic NOD mice are able to suppress the proliferation of CD4+ CD25- cells to a similar extent in vitro. We also found that pretreatment of NOD mice with anti-CD25 antibody allowed T cells with a known reactivity to islet antigen to proliferate more in the pancreatic draining lymph nodes of NOD mice, regardless of age. In addition, we demonstrated that onset of diabetes in NOD.scid mice is faster when recipients are co-administered splenocytes from diabetic NOD donors and anti-CD25. Finally, we found that although diabetic CD4+ CD25+ T cells are not as suppressive in cotransfers with effectors into NOD.scid recipients, this may not indicate a decline in Treg function in diabetic mice because over 10% of CD4+ CD25+ T cells are non-Foxp3 and the phenotype of the CD25- contaminating population significantly differs in non-diabetic and diabetic mice. This work questions whether onset of diabetes in NOD mice is associated with a decline in Treg function.
Original languageEnglish
Pages (from-to)15-28
Number of pages14
JournalImmunology
Volume121
Issue number1
DOIs
Publication statusPublished - May 2007

Keywords

  • Adoptive Transfer
  • Aging
  • Animals
  • Autoantigens
  • Cell Proliferation
  • Cells, Cultured
  • Diabetes Mellitus, Experimental
  • Forkhead Transcription Factors
  • Immune Tolerance
  • Immunophenotyping
  • Interleukin-2 Receptor alpha Subunit
  • Islets of Langerhans
  • Lymph Nodes
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Spleen
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Regulatory

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