HLA-DR*0401 expression in the NOD mice prevents the development of autoimmune diabetes by multiple alterations in the T-cell compartment

Luis Pow Sang, Jacqueline Surls, Mirian Mendoza, Sofia Casares, Teodor Brumeanu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Several human HLA alleles have been found associated with type 1 diabetes (T1D), but their precise role is not clearly defined. Herein, we report that a human MHC class II (HLA-DR*0401) allele transgene that has been expressed into NOD (H-2g7I-Enull) mice prone to T1D rendered the mice resistant to the disease. T1D resistance occurred in the context of multi-point T-cell alterations such as: (i) skewed CD4/CD8 T-cell ratio, (ii) decreased size of CD4+CD44high T memory pool, (iii) aberrant TCR Vβ repertoire, (iv) increased neonatal number of Foxp3+ and TR-1+ regulatory cells, and (v) reduced IFN-γ inflammatory response vs. enhanced IL-10 suppressogenic response of T-cells upon polyclonal and antigen-specific stimulation. The T-cells from NOD/DR4 Tg mice were unable to induce or suppress diabetes in NOD/RAG deficient mice. This study describes a multifaceted regulatory function of the HLA-DR*0401 allele strongly associated with the lack of T1D development in NOD mice.

Original languageEnglish
Pages (from-to)54-65
Number of pages12
JournalCellular Immunology
Volume298
Issue number1-2
DOIs
StatePublished - 1 Nov 2015
Externally publishedYes

Keywords

  • 0401
  • HLA-DR
  • NOD humanized mice
  • T-cell regulation
  • Type 1 diabetes

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