| First Author | Pow Sang L | Year | 2015 |
| Journal | Cell Immunol | Volume | 298 |
| Issue | 1-2 | Pages | 54-65 |
| PubMed ID | 26363521 | Mgi Jnum | J:233732 |
| Mgi Id | MGI:5787904 | Doi | 10.1016/j.cellimm.2015.09.003 |
| Citation | Pow Sang L, et al. (2015) HLA-DR*0401 expression in the NOD mice prevents the development of autoimmune diabetes by multiple alterations in the T-cell compartment. Cell Immunol 298(1-2):54-65 |
| abstractText | 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-2(g7)I-E(null)) 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(+)CD44(high) T memory pool, (iii) aberrant TCR Vbeta repertoire, (iv) increased neonatal number of Foxp3(+) and TR-1(+) regulatory cells, and (v) reduced IFN-gamma 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. |
