Faculty Research 1990 - 1999


Quantitative thresholds of MHC class II I-E expressed on hemopoietically derived antigen-presenting cells in transgenic NOD/Lt mice determine level of diabetes resistance and indicate mechanism of protection.

Document Type


Publication Date



Animal, Antigen-Presenting-Cells: im, Autoantigens: im, Blotting-Northern, Deoxyribonuclease-HindIII: me, Diabetes-Mellitus-Insulin-Dependent: im, Enzyme-Linked-Immunosorbent-Assay, Female, Flow-Cytometry, Glutamate-Decarboxylase: im, Histocompatibility-Antigens-Class-II: bi, im, Immunity-Natural: im, Interleukin-4: bi, Male, Mice, Mice-Inbred-BALB-C, Mice-Inbred-NOD, Mice-Transgenic, Molecular-Sequence-Data, Polymerase-Chain-Reaction, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: im, Transgenes: ge

JAX Source

J Immunol 1996 Aug 1;157(3):1279-87




Two homozygous lines of transgenic NOD/Lt mice expressing MHC class II I-E molecules at quantitatively different levels were utilized to study mechanisms of I-E-mediated diabetes prevention. In line 12, I-E expression on APC at levels comparable with that in BALB/cByJ controls conferred only partial diabetes resistance. In line 5, greater than normal I-E levels on APC correlated with nearly complete resistance. Levels of endogenously encoded I-Ag7 correlated inversely with transgene-induced I-E expression. T cell transfer experiments into NOD/severe combined immunodeficient mice demonstrated the presence of pathogenic T cells in I-E+ donors, and that continuous expression of I-E on hemopoietically derived APC was required to block their pathogenic function. T cells from transgenic and nontransgenic NOD/Lt mice primed in vivo against the beta cell autoantigen 65-kDa isoform of glutamic acid decarboxylase (GAD65) and two peptides derived from this protein proliferated when restimulated in vitro. However, reverse-transcription PCR and ELISA measurements of cytokine mRNA and protein levels showed that the GAD65-reactive T cells from both line 5 and line 12 mice produced higher levels of IL-4 and lower levels of IFN-gamma than similar T cells from standard NOD/Lt mice. Thus, the inverse relationship between I-E and I-Ag7 expression was associated with qualitative differences in T cell responses to putative beta cell autoantigens. Collectively, these data indicate quantitative increases in I-E expression on APC may block insulin-dependent diabetes mellitus by altering the balance of cytokines produced by beta cell autoreactive T cells.